[Frontiers in Bioscience, Landmark, 25, 838-873, Jan 1, 2020]

Epithelial to mesenchymal plasticity: role in cancer progression

Remya Raja1,3, Akhilesh Pandey1-5, Prashant Kumar1-3

1Institute of Bioinformatics, International Technology Park, Bangalore, 560066, India, 2Centre for Molecular Medicine, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, 560029, India, 3Manipal Academy of Higher Education (MAHE), Manipal, 576104, India, 4Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN55905, US, 5Center for Individualized Medicine, Mayo Clinic, Rochester, MN55905, US

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Epithelial to mesenchymal transition
    3.1. Overview of EMT
4. EMT in cancer
    4.1. EMT in cell survival, resistance to anoikis and acquisition of stem cell-like characteristics
    4.2. EMT and chemoresistance
    4.3. Role of stromal compartment in regulating EMT in primary tumor
    4.4. EMT and immune evasion
    4.5. EMT and metastasis
5. Circulating tumor cells in cancer
    5.1. EMT in CTC
    5.2. Role of stroma in regulating EMT in CTC
    5.3. EMT signatures associated with CTC
    5.4. Clinical perspectives of CTC
6. Future direction
7. Acknowledgments
8. References

1. ABSTRACT

Epithelial-mesenchymal transition (EMT) is a dynamic process by which the cells transdifferentiate into two or more somatic states. The metastatic spread begins with tumor cells disseminated from the primary tumor via intravasation, hematogenous transit and extravasation to reach the distant organs to form micro- or macrometastasis. Dissemination of tumor cells or metastasis is a crucial stage in cancer progression and accounts for majority of cancer associated morbidity and mortality. Advances in technology has now enabled detection and capture of tumor cells that escape from primary site into the bloodstream. Such tumor cells which are found in transit in the blood are referred to as circulating tumor cells (CTCs) and they represent the early step in metastatic cascade. The dynamic changes in EMT phenotype in CTCs plays a key role in cancer metastasis. This review will focus on the role of EMT in cancer progression, circulating tumor cells and its clinical relevance.

8. REFERENCES

1. D. M. Gonzalez and D. Medici: Signaling mechanisms of the epithelial-mesenchymal transition. Sci Signal, 7(344), re8 (2014)
DOI: 10.1126/scisignal.2005189

2. J. Yang and R. A. Weinberg: Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell, 14(6), 818-29 (2008)
DOI: 10.1016/j.devcel.2008.05.009

3. S. Lamouille, J. Xu and R. Derynck: Molecular mechanisms of epithelial-mesenchymal transition. Nat Rev Mol Cell Biol, 15(3), 178-96 (2014)
DOI: 10.1038/nrm3758

4. N. Skrypek, S. Goossens, E. De Smedt, N. Vandamme and G. Berx: Epithelial-to-Mesenchymal Transition: Epigenetic Reprogramming Driving Cellular Plasticity. Trends Genet, 33(12), 943-959 (2017)
DOI: 10.1016/j.tig.2017.08.004

5. A. Zaravinos: The Regulatory Role of MicroRNAs in EMT and Cancer. J Oncol, 2015, 865816 (2015)
DOI: 10.1155/2015/865816

6. G. Manzo: Similarities Between Embryo Development and Cancer Process Suggest New Strategies for Research and Therapy of Tumors: A New Point of View. Front Cell Dev Biol, 7, 20 (2019)
DOI: 10.3389/fcell.2019.00020

7. M. A. Nieto: Epithelial plasticity: a common theme in embryonic and cancer cells. Science, 342(6159), 1234850 (2013)
DOI: 10.1126/science.1234850

8. J. P. Thiery: Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer, 2(6), 442-54 (2002)
DOI: 10.1038/nrc822

9. X. Ye and R. A. Weinberg: Epithelial-Mesenchymal Plasticity: A Central Regulator of Cancer Progression. Trends Cell Biol, 25(11), 675-686 (2015)
DOI: 10.1016/j.tcb.2015.07.012

10. J. P. Thiery, H. Acloque, R. Y. Huang and M. A. Nieto: Epithelial-mesenchymal transitions in development and disease. Cell, 139(5), 871-90 (2009)
DOI: 10.1016/j.cell.2009.11.007

11. A. D. Grigore, M. K. Jolly, D. Jia, M. C. Farach-Carson and H. Levine: Tumor Budding: The Name is EMT. Partial EMT. J Clin Med, 5(5) (2016)
DOI: 10.3390/jcm5050051

12. M. A. Nieto, R. Y. Huang, R. A. Jackson and J. P. Thiery: Emt: 2016. Cell, 166(1), 21-45 (2016)
DOI: 10.1016/j.cell.2016.06.028

13. M. Saitoh: Involvement of partial EMT in cancer progression. J Biochem, 164(4), 257-264 (2018)
DOI: 10.1093/jb/mvy047

14. V. Fustaino, D. Presutti, T. Colombo, B. Cardinali, G. Papoff, R. Brandi, P. Bertolazzi, G. Felici and G. Ruberti: Characterization of epithelial-mesenchymal transition intermediate/hybrid phenotypes associated to resistance to EGFR inhibitors in non-small cell lung cancer cell lines. Oncotarget, 8(61), 103340-103363 (2017)
DOI: 10.18632/oncotarget.21132

15. M. T. Grande, B. Sanchez-Laorden, C. Lopez-Blau, C. A. De Frutos, A. Boutet, M. Arevalo, R. G. Rowe, S. J. Weiss, J. M. Lopez-Novoa and M. A. Nieto: Snail1-induced partial epithelial-to-mesenchymal transition drives renal fibrosis in mice and can be targeted to reverse established disease. Nat Med, 21(9), 989-97 (2015)
DOI: 10.1038/nm.3901

16. M. K. Jolly, M. Boareto, B. Huang, D. Jia, M. Lu, E. Ben-Jacob, J. N. Onuchic and H. Levine: Implications of the Hybrid Epithelial/Mesenchymal Phenotype in Metastasis. Front Oncol, 5, 155 (2015)
DOI: 10.3389/fonc.2015.00155

17. M. Yu, A. Bardia, B. S. Wittner, S. L. Stott, M. E. Smas, D. T. Ting, S. J. Isakoff, J. C. Ciciliano, M. N. Wells, A. M. Shah, K. F. Concannon, M. C. Donaldson, L. V. Sequist, E. Brachtel, D. Sgroi, J. Baselga, S. Ramaswamy, M. Toner, D. A. Haber and S. Maheswaran: Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition. Science, 339(6119), 580-4 (2013)
DOI: 10.1126/science.1228522

18. C. Alix-Panabieres and K. Pantel: Circulating tumor cells: liquid biopsy of cancer. Clin Chem, 59(1), 110-8 (2013)
DOI: 10.1373/clinchem.2012.194258

19. M. A. Papadaki, G. Stoupis, P. A. Theodoropoulos, D. Mavroudis, V. Georgoulias and S. Agelaki: Circulating Tumor Cells with Stemness and Epithelial-to-Mesenchymal Transition Features Are Chemoresistant and Predictive of Poor Outcome in Metastatic Breast Cancer. Mol Cancer Ther, 18(2), 437-447 (2019)
DOI: 10.1158/1535-7163.MCT-18-0584

20. G. Greenburg and E. D. Hay: Epithelia suspended in collagen gels can lose polarity and express characteristics of migrating mesenchymal cells. J Cell Biol, 95(1), 333-9 (1982)

21. E. D. Hay: The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it. Dev Dyn, 233(3), 706-20 (2005)
DOI: 10.1002/dvdy.20345

22. U. W. Rothenpieler and G. R. Dressler: Pax-2 is required for mesenchyme-to-epithelium conversion during kidney development. Development, 119(3), 711-20 (1993)

23. A. M. Valles, B. Boyer, J. Badet, G. C. Tucker, D. Barritault and J. P. Thiery: Acidic fibroblast growth factor is a modulator of epithelial plasticity in a rat bladder carcinoma cell line. Proc Natl Acad Sci U S A, 87(3), 1124-8 (1990)

24. R. Kalluri and E. G. Neilson: Epithelial-mesenchymal transition and its implications for fibrosis. J Clin Invest, 112(12), 1776-84 (2003)
DOI: 10.1172/JCI20530

25. R. Kalluri and R. A. Weinberg: The basics of epithelial-mesenchymal transition. J Clin Invest, 119(6), 1420-8 (2009)
DOI: 10.1172/JCI39104

26. H. Peinado, F. Portillo and A. Cano: Transcriptional regulation of cadherins during development and carcinogenesis. Int J Dev Biol, 48(5-6), 365-75 (2004)
DOI: 10.1387/ijdb.041794hp

27. P. Nistico, M. J. Bissell and D. C. Radisky: Epithelial-mesenchymal transition: general principles and pathological relevance with special emphasis on the role of matrix metalloproteinases. Cold Spring Harb Perspect Biol, 4(2) (2012)
DOI: 10.1101/cshperspect.a011908

28. R. Y. Huang, P. Guilford and J. P. Thiery: Early events in cell adhesion and polarity during epithelial-mesenchymal transition. J Cell Sci, 125(Pt 19), 4417-22 (2012)
DOI: 10.1242/jcs.099697

29. A. J. Knights, A. P. Funnell, M. Crossley and R. C. Pearson: Holding Tight: Cell Junctions and Cancer Spread. Trends Cancer Res, 8, 61-69 (2012)

30. M. G. Chun and D. Hanahan: Genetic deletion of the desmosomal component desmoplakin promotes tumor microinvasion in a mouse model of pancreatic neuroendocrine carcinogenesis. PLoS Genet, 6(9), e1001120 (2010)
DOI: 10.1371/journal.pgen.1001120

31. J. Ikenouchi, M. Matsuda, M. Furuse and S. Tsukita: Regulation of tight junctions during the epithelium-mesenchyme transition: direct repression of the gene expression of claudins/occludin by Snail. J Cell Sci, 116(Pt 10), 1959-67 (2003)
DOI: 10.1242/jcs.00389

32. B. V. Kallakury, C. E. Sheehan and J. S. Ross: Co-downregulation of cell adhesion proteins alpha- and beta-catenins, p120CTN, E-cadherin, and CD44 in prostatic adenocarcinomas. Hum Pathol, 32(8), 849-55 (2001)
DOI: 10.1053/hupa.2001.26463

33. B. Boyer and J. P. Thiery: Epithelium-mesenchyme interconversion as example of epithelial plasticity. APMIS, 101(4), 257-68 (1993)

34. E. D. Hay: An overview of epithelio-mesenchymal transformation. Acta Anat (Basel), 154(1), 8-20 (1995)

35. M. Zeisberg and E. G. Neilson: Biomarkers for epithelial-mesenchymal transitions. J Clin Invest, 119(6), 1429-37 (2009)
DOI: 10.1172/JCI36183

36. D. Tarin, E. W. Thompson and D. F. Newgreen: The fallacy of epithelial mesenchymal transition in neoplasia. Cancer Res, 65(14), 5996-6000; discussion 6000-1 (2005)
DOI: 10.1158/0008-5472.CAN-05-0699

37. G. Sannino, A. Marchetto, T. Kirchner and T. G. P. Grunewald: Epithelial-to-Mesenchymal and Mesenchymal-to-Epithelial Transition in Mesenchymal Tumors: A Paradox in Sarcomas? Cancer Res, 77(17), 4556-4561 (2017)
DOI: 10.1158/0008-5472.CAN-17-0032

38. B. T. Hennessy, A. M. Gonzalez-Angulo, K. Stemke-Hale, M. Z. Gilcrease, S. Krishnamurthy, J. S. Lee, J. Fridlyand, A. Sahin, R. Agarwal, C. Joy, W. Liu, D. Stivers, K. Baggerly, M. Carey, A. Lluch, C. Monteagudo, X. He, V. Weigman, C. Fan, J. Palazzo, G. N. Hortobagyi, L. K. Nolden, N. J. Wang, V. Valero, J. W. Gray, C. M. Perou and G. B. Mills: Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res, 69(10), 4116-24 (2009)
DOI: 10.1158/0008-5472.CAN-08-3441

39. D. Sarrio, S. M. Rodriguez-Pinilla, D. Hardisson, A. Cano, G. Moreno-Bueno and J. Palacios: Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype. Cancer Res, 68(4), 989-97 (2008)
DOI: 10.1158/0008-5472.CAN-07-2017

40. A. Gradilone, C. Raimondi, C. Nicolazzo, A. Petracca, O. Gandini, B. Vincenzi, G. Naso, A. M. Agliano, E. Cortesi and P. Gazzaniga: Circulating tumour cells lacking cytokeratin in breast cancer: the importance of being mesenchymal. J Cell Mol Med, 15(5), 1066-70 (2011)
DOI: 10.1111/j.1582-4934.2011.01285.x

41. A. D. Rhim, E. T. Mirek, N. M. Aiello, A. Maitra, J. M. Bailey, F. McAllister, M. Reichert, G. L. Beatty, A. K. Rustgi, R. H. Vonderheide, S. D. Leach and B. Z. Stanger: EMT and dissemination precede pancreatic tumor formation. Cell, 148(1-2), 349-61 (2012)
DOI: 10.1016/j.cell.2011.11.025

42. A. J. Trimboli, K. Fukino, A. de Bruin, G. Wei, L. Shen, S. M. Tanner, N. Creasap, T. J. Rosol, M. L. Robinson, C. Eng, M. C. Ostrowski and G. Leone: Direct evidence for epithelial-mesenchymal transitions in breast cancer. Cancer Res, 68(3), 937-45 (2008)
DOI: 10.1158/0008-5472.CAN-07-2148

43. T. Brabletz, A. Jung, S. Reu, M. Porzner, F. Hlubek, L. A. Kunz-Schughart, R. Knuechel and T. Kirchner: Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Natl Acad Sci U S A, 98(18), 10356-61 (2001)
DOI: 10.1073/pnas.171610498

44. P. Navarro, E. Lozano and A. Cano: Expression of E- or P-cadherin is not sufficient to modify the morphology and the tumorigenic behavior of murine spindle carcinoma cells. Possible involvement of plakoglobin. J Cell Sci, 105 ( Pt 4), 923-34 (1993)

45. K. Chu, K. M. Boley, R. Moraes, S. H. Barsky and F. M. Robertson: The paradox of E-cadherin: role in response to hypoxia in the tumor microenvironment and regulation of energy metabolism. Oncotarget, 4(3), 446-62 (2013)
DOI: 10.18632/oncotarget.872

46. K. Blechschmidt, S. Sassen, B. Schmalfeldt, T. Schuster, H. Hofler and K. F. Becker: The E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients. Br J Cancer, 98(2), 489-95 (2008)
DOI: 10.1038/sj.bjc.6604115

47. S. Elloul, M. B. Elstrand, J. M. Nesland, C. G. Trope, G. Kvalheim, I. Goldberg, R. Reich and B. Davidson: Snail, Slug, and Smad-interacting protein 1 as novel parameters of disease aggressiveness in metastatic ovarian and breast carcinoma. Cancer, 103(8), 1631-43 (2005)
DOI: 10.1002/cncr.20946

48. I. Gomez, C. Pena, M. Herrera, C. Munoz, M. J. Larriba, V. Garcia, G. Dominguez, J. Silva, R. Rodriguez, A. Garcia de Herreros, F. Bonilla and J. M. Garcia: TWIST1 is expressed in colorectal carcinomas and predicts patient survival. PLoS One, 6(3), e18023 (2011)
DOI: 10.1371/journal.pone.0018023

49. J. Grzegrzolka, M. Biala, P. Wojtyra, C. Kobierzycki, M. Olbromski, A. Gomulkiewicz, A. Piotrowska, J. Rys, M. Podhorska-Okolow and P. Dziegiel: Expression of EMT Markers SLUG and TWIST in Breast Cancer. Anticancer Res, 35(7), 3961-8 (2015)

50. S. Muenst, S. Daster, E. C. Obermann, R. A. Droeser, W. P. Weber, U. von Holzen, F. Gao, C. Viehl, D. Oertli and S. D. Soysal: Nuclear expression of snail is an independent negative prognostic factor in human breast cancer. Dis Markers, 35(5), 337-44 (2013)
DOI: 10.1155/2013/902042

51. M. Shioiri, T. Shida, K. Koda, K. Oda, K. Seike, M. Nishimura, S. Takano and M. Miyazaki: Slug expression is an independent prognostic parameter for poor survival in colorectal carcinoma patients. Br J Cancer, 94(12), 1816-22 (2006)
DOI: 10.1038/sj.bjc.6603193

52. A. Yusup, B. Huji, C. Fang, F. Wang, T. Dadihan, H. J. Wang and H. Upur: Expression of trefoil factors and TWIST1 in colorectal cancer and their correlation with metastatic potential and prognosis. World J Gastroenterol, 23(1), 110-120 (2017)
DOI: 10.3748/wjg.v23.i1.110

53. H. E. Rashed, S. Hussein, H. Mosaad, M. M. Abdelwahab, M. I. Abdelhamid, S. Y. Mohamed, A. M. Mohamed and A. Fayed: Prognostic significance of the genetic and the immunohistochemical expression of epithelial-mesenchymal-related markers in colon cancer. Cancer Biomark, 20(1), 107-122 (2017)
DOI: 10.3233/CBM-170034

54. S. E. Moody, D. Perez, T. C. Pan, C. J. Sarkisian, C. P. Portocarrero, C. J. Sterner, K. L. Notorfrancesco, R. D. Cardiff and L. A. Chodosh: The transcriptional repressor Snail promotes mammary tumor recurrence. Cancer Cell, 8(3), 197-209 (2005)
DOI: 10.1016/j.ccr.2005.07.009

55. C. Martinez-Ciarpaglini, S. Oltra, S. Rosello, D. Roda, C. Mongort, F. Carrasco, J. Gonzalez, F. Santonja, N. Tarazona, M. Huerta, A. Espi, G. Ribas, A. Ferrandez, S. Navarro and A. Cervantes: Low miR200c expression in tumor budding of invasive front predicts worse survival in patients with localized colon cancer and is related to PD-L1 overexpression. Mod Pathol, 32(2), 306-313 (2019)
DOI: 10.1038/s41379-018-0124-5

56. N. Tiwari, A. Gheldof, M. Tatari and G. Christofori: EMT as the ultimate survival mechanism of cancer cells. Semin Cancer Biol, 22(3), 194-207 (2012)
DOI: 10.1016/j.semcancer.2012.02.013

57. A. Inoue, M. G. Seidel, W. Wu, S. Kamizono, A. A. Ferrando, R. T. Bronson, H. Iwasaki, K. Akashi, A. Morimoto, J. K. Hitzler, T. I. Pestina, C. W. Jackson, R. Tanaka, M. J. Chong, P. J. McKinnon, T. Inukai, G. C. Grosveld and A. T. Look: Slug, a highly conserved zinc finger transcriptional repressor, protects hematopoietic progenitor cells from radiation-induced apoptosis in vivo. Cancer Cell, 2(4), 279-88 (2002)

58. M. Kajita, K. N. McClinic and P. A. Wade: Aberrant expression of the transcription factors snail and slug alters the response to genotoxic stress. Mol Cell Biol, 24(17), 7559-66 (2004)
DOI: 10.1128/MCB.24.17.7559-7566.2004

59. W. S. Wu, S. Heinrichs, D. Xu, S. P. Garrison, G. P. Zambetti, J. M. Adams and A. T. Look: Slug antagonizes p53-mediated apoptosis of hematopoietic progenitors by repressing puma. Cell, 123(4), 641-53 (2005)
DOI: 10.1016/j.cell.2005.09.029

60. S. Vega, A. V. Morales, O. H. Ocana, F. Valdes, I. Fabregat and M. A. Nieto: Snail blocks the cell cycle and confers resistance to cell death. Genes Dev, 18(10), 1131-43 (2004)
DOI: 10.1101/gad.294104

61. Y. Wu and B. P. Zhou: Snail: More than EMT. Cell Adh Migr, 4(2), 199-203 (2010)

62. M. Escriva, S. Peiro, N. Herranz, P. Villagrasa, N. Dave, B. Montserrat-Sentis, S. A. Murray, C. Franci, T. Gridley, I. Virtanen and A. Garcia de Herreros: Repression of PTEN phosphatase by Snail1 transcriptional factor during gamma radiation-induced apoptosis. Mol Cell Biol, 28(5), 1528-40 (2008)
DOI: 10.1128/MCB.02061-07

63. N. K. Kurrey, S. P. Jalgaonkar, A. V. Joglekar, A. D. Ghanate, P. D. Chaskar, R. Y. Doiphode and S. A. Bapat: Snail and slug mediate radioresistance and chemoresistance by antagonizing p53-mediated apoptosis and acquiring a stem-like phenotype in ovarian cancer cells. Stem Cells, 27(9), 2059-68 (2009)
DOI: 10.1002/stem.154

64. J. Mejlvang, M. Kriajevska, C. Vandewalle, T. Chernova, A. E. Sayan, G. Berx, J. K. Mellon and E. Tulchinsky: Direct repression of cyclin D1 by SIP1 attenuates cell cycle progression in cells undergoing an epithelial mesenchymal transition. Mol Biol Cell, 18(11), 4615-24 (2007)
DOI: 10.1091/mbc.e07-05-0406

65. G. Fontemaggi, A. Gurtner, S. Strano, Y. Higashi, A. Sacchi, G. Piaggio and G. Blandino: The transcriptional repressor ZEB regulates p73 expression at the crossroad between proliferation and differentiation. Mol Cell Biol, 21(24), 8461-70 (2001)
DOI: 10.1128/MCB.21.24.8461-8470.2001

66. S. Valsesia-Wittmann, M. Magdeleine, S. Dupasquier, E. Garin, A. C. Jallas, V. Combaret, A. Krause, P. Leissner and A. Puisieux: Oncogenic cooperation between H-Twist and N-Myc overrides failsafe programs in cancer cells. Cancer Cell, 6(6), 625-30 (2004)
DOI: 10.1016/j.ccr.2004.09.033

67. Z. Cao, T. Livas and N. Kyprianou: Anoikis and EMT: Lethal "Liaisons" during Cancer Progression. Crit Rev Oncog, 21(3-4), 155-168 (2016)
DOI: 10.1615/CritRevOncog.2016016955

68. A. Barrallo-Gimeno and M. A. Nieto: The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development, 132(14), 3151-61 (2005)
DOI: 10.1242/dev.01907

69. K. Orford, C. C. Orford and S. W. Byers: Exogenous expression of beta-catenin regulates contact inhibition, anchorage-independent growth, anoikis, and radiation-induced cell cycle arrest. J Cell Biol, 146(4), 855-68 (1999)

70. Y. Takeyama, M. Sato, M. Horio, T. Hase, K. Yoshida, T. Yokoyama, H. Nakashima, N. Hashimoto, Y. Sekido, A. F. Gazdar, J. D. Minna, M. Kondo and Y. Hasegawa: Knockdown of ZEB1, a master epithelial-to-mesenchymal transition (EMT) gene, suppresses anchorage-independent cell growth of lung cancer cells. Cancer Lett, 296(2), 216-24 (2010)
DOI: 10.1016/j.canlet.2010.04.008

71. S. Ansieau, J. Bastid, A. Doreau, A. P. Morel, B. P. Bouchet, C. Thomas, F. Fauvet, I. Puisieux, C. Doglioni, S. Piccinin, R. Maestro, T. Voeltzel, A. Selmi, S. Valsesia-Wittmann, C. Caron de Fromentel and A. Puisieux: Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence. Cancer Cell, 14(1), 79-89 (2008)
DOI: 10.1016/j.ccr.2008.06.005

72. Y. Liu, S. El-Naggar, D. S. Darling, Y. Higashi and D. C. Dean: Zeb1 links epithelial-mesenchymal transition and cellular senescence. Development, 135(3), 579-88 (2008)
DOI: 10.1242/dev.007047

73. S. A. Mani, W. Guo, M. J. Liao, E. N. Eaton, A. Ayyanan, A. Y. Zhou, M. Brooks, F. Reinhard, C. C. Zhang, M. Shipitsin, L. L. Campbell, K. Polyak, C. Brisken, J. Yang and R. A. Weinberg: The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell, 133(4), 704-15 (2008)
DOI: 10.1016/j.cell.2008.03.027

74. C. J. Chang, C. H. Chao, W. Xia, J. Y. Yang, Y. Xiong, C. W. Li, W. H. Yu, S. K. Rehman, J. L. Hsu, H. H. Lee, M. Liu, C. T. Chen, D. Yu and M. C. Hung: p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs. Nat Cell Biol, 13(3), 317-23 (2011)
DOI: 10.1038/ncb2173

75. U. Wellner, J. Schubert, U. C. Burk, O. Schmalhofer, F. Zhu, A. Sonntag, B. Waldvogel, C. Vannier, D. Darling, A. zur Hausen, V. G. Brunton, J. Morton, O. Sansom, J. Schuler, M. P. Stemmler, C. Herzberger, U. Hopt, T. Keck, S. Brabletz and T. Brabletz: The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs. Nat Cell Biol, 11(12), 1487-95 (2009)
DOI: 10.1038/ncb1998

76. D. Kong, S. Banerjee, A. Ahmad, Y. Li, Z. Wang, S. Sethi and F. H. Sarkar: Epithelial to mesenchymal transition is mechanistically linked with stem cell signatures in prostate cancer cells. PLoS One, 5(8), e12445 (2010)
DOI: 10.1371/journal.pone.0012445

77. M. H. Yang, D. S. Hsu, H. W. Wang, H. J. Wang, H. Y. Lan, W. H. Yang, C. H. Huang, S. Y. Kao, C. H. Tzeng, S. K. Tai, S. Y. Chang, O. K. Lee and K. J. Wu: Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition. Nat Cell Biol, 12(10), 982-92 (2010)
DOI: 10.1038/ncb2099

78. W. H. Yang, H. Y. Lan, C. H. Huang, S. K. Tai, C. H. Tzeng, S. Y. Kao, K. J. Wu, M. C. Hung and M. H. Yang: RAC1 activation mediates Twist1-induced cancer cell migration. Nat Cell Biol, 14(4), 366-74 (2012)
DOI: 10.1038/ncb2455

79. T. T. Liao, W. H. Hsu, C. H. Ho, W. L. Hwang, H. Y. Lan, T. Lo, C. C. Chang, S. K. Tai and M. H. Yang: let-7 Modulates Chromatin Configuration and Target Gene Repression through Regulation of the ARID3B Complex. Cell Rep, 14(3), 520-533 (2016)
DOI: 10.1016/j.celrep.2015.12.064

80. W. Guo, Z. Keckesova, J. L. Donaher, T. Shibue, V. Tischler, F. Reinhardt, S. Itzkovitz, A. Noske, U. Zurrer-Hardi, G. Bell, W. L. Tam, S. A. Mani, A. van Oudenaarden and R. A. Weinberg: Slug and Sox9 cooperatively determine the mammary stem cell state. Cell, 148(5), 1015-28 (2012)
DOI: 10.1016/j.cell.2012.02.008

81. W. L. Hwang, J. K. Jiang, S. H. Yang, T. S. Huang, H. Y. Lan, H. W. Teng, C. Y. Yang, Y. P. Tsai, C. H. Lin, H. W. Wang and M. H. Yang: MicroRNA-146a directs the symmetric division of Snail-dominant colorectal cancer stem cells. Nat Cell Biol, 16(3), 268-80 (2014)
DOI: 10.1038/ncb2910

82. T. T. Liao and M. H. Yang: Revisiting epithelial-mesenchymal transition in cancer metastasis: the connection between epithelial plasticity and stemness. Mol Oncol, 11(7), 792-804 (2017)
DOI: 10.1002/1878-0261.12096

83. O. H. Ocana, R. Corcoles, A. Fabra, G. Moreno-Bueno, H. Acloque, S. Vega, A. Barrallo-Gimeno, A. Cano and M. A. Nieto: Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell, 22(6), 709-24 (2012)
DOI: 10.1016/j.ccr.2012.10.012

84. J. M. Schmidt, E. Panzilius, H. S. Bartsch, M. Irmler, J. Beckers, V. Kari, J. R. Linnemann, D. Dragoi, B. Hirschi, U. J. Kloos, S. Sass, F. Theis, S. Kahlert, S. A. Johnsen, K. Sotlar and C. H. Scheel: Stem-cell-like properties and epithelial plasticity arise as stable traits after transient Twist1 activation. Cell Rep, 10(2), 131-9 (2015)
DOI: 10.1016/j.celrep.2014.12.032

85. T. Celia-Terrassa, O. Meca-Cortes, F. Mateo, A. Martinez de Paz, N. Rubio, A. Arnal-Estape, B. J. Ell, R. Bermudo, A. Diaz, M. Guerra-Rebollo, J. J. Lozano, C. Estaras, C. Ulloa, D. Alvarez-Simon, J. Mila, R. Vilella, R. Paciucci, M. Martinez-Balbas, A. G. de Herreros, R. R. Gomis, Y. Kang, J. Blanco, P. L. Fernandez and T. M. Thomson: Epithelial-mesenchymal transition can suppress major attributes of human epithelial tumor-initiating cells. J Clin Invest, 122(5), 1849-68 (2012)
DOI: 10.1172/JCI59218

86. Q. Meng, S. Shi, C. Liang, D. Liang, J. Hua, B. Zhang, J. Xu and X. Yu: Abrogation of glutathione peroxidase-1 drives EMT and chemoresistance in pancreatic cancer by activating ROS-mediated Akt/GSK3beta/Snail signaling. Oncogene, 37(44), 5843-5857 (2018)
DOI: 10.1038/s41388-018-0392-z

87. J. van Staalduinen, D. Baker, P. Ten Dijke and H. van Dam: Epithelial-mesenchymal-transition-inducing transcription factors: new targets for tackling chemoresistance in cancer? Oncogene (2018)
DOI: 10.1038/s41388-018-0378-x

88. K. R. Fischer, A. Durrans, S. Lee, J. Sheng, F. Li, S. T. Wong, H. Choi, T. El Rayes, S. Ryu, J. Troeger, R. F. Schwabe, L. T. Vahdat, N. K. Altorki, V. Mittal and D. Gao: Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistance. Nature, 527(7579), 472-6 (2015)
DOI: 10.1038/nature15748

89. X. Zheng, J. L. Carstens, J. Kim, M. Scheible, J. Kaye, H. Sugimoto, C. C. Wu, V. S. LeBleu and R. Kalluri: Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancer. Nature, 527(7579), 525-530 (2015)
DOI: 10.1038/nature16064

90. M. Saxena, M. A. Stephens, H. Pathak and A. Rangarajan: Transcription factors that mediate epithelial-mesenchymal transition lead to multidrug resistance by upregulating ABC transporters. Cell Death Dis, 2, e179 (2011)
DOI: 10.1038/cddis.2011.61

91. D. Y. Rhyu, Y. Yang, H. Ha, G. T. Lee, J. S. Song, S. T. Uh and H. B. Lee: Role of reactive oxygen species in TGF-beta1-induced mitogen-activated protein kinase activation and epithelial-mesenchymal transition in renal tubular epithelial cells. J Am Soc Nephrol, 16(3), 667-75 (2005)
DOI: 10.1681/ASN.2004050425

92. G. Zhou, L. A. Dada, M. Wu, A. Kelly, H. Trejo, Q. Zhou, J. Varga and J. I. Sznajder: Hypoxia-induced alveolar epithelial-mesenchymal transition requires mitochondrial ROS and hypoxia-inducible factor 1. Am J Physiol Lung Cell Mol Physiol, 297(6), L1120-30 (2009)
DOI: 10.1152/ajplung.00007.2009

93. D. Nantajit, D. Lin and J. J. Li: The network of epithelial-mesenchymal transition: potential new targets for tumor resistance. J Cancer Res Clin Oncol, 141(10), 1697-713 (2015)
DOI: 10.1007/s00432-014-1840-y

94. J. Kirshner, M. F. Jobling, M. J. Pajares, S. A. Ravani, A. B. Glick, M. J. Lavin, S. Koslov, Y. Shiloh and M. H. Barcellos-Hoff: Inhibition of transforming growth factor-beta1 signaling attenuates ataxia telangiectasia mutated activity in response to genotoxic stress. Cancer Res, 66(22), 10861-9 (2006)
DOI: 10.1158/0008-5472.CAN-06-2565

95. V. Comaills, L. Kabeche, R. Morris, R. Buisson, M. Yu, M. W. Madden, J. A. LiCausi, M. Boukhali, K. Tajima, S. Pan, N. Aceto, S. Sil, Y. Zheng, T. Sundaresan, T. Yae, N. V. Jordan, D. T. Miyamoto, D. T. Ting, S. Ramaswamy, W. Haas, L. Zou, D. A. Haber and S. Maheswaran: Genomic Instability Is Induced by Persistent Proliferation of Cells Undergoing Epithelial-to-Mesenchymal Transition. Cell Rep, 17(10), 2632-2647 (2016)
DOI: 10.1016/j.celrep.2016.11.022

96. V. Krishnan, Y. L. Chong, T. Z. Tan, M. Kulkarni, M. B. Bin Rahmat, L. S. Tay, H. Sankar, D. S. Jokhun, A. Ganesan, L. S. H. Chuang, D. C. Voon, G. V. Shivashankar, J. P. Thiery and Y. Ito: TGFbeta Promotes Genomic Instability after Loss of RUNX3. Cancer Res, 78(1), 88-102 (2018)
DOI: 10.1158/0008-5472.CAN-17-1178

97. B. Psaila and D. Lyden: The metastatic niche: adapting the foreign soil. Nat Rev Cancer, 9(4), 285-93 (2009)
DOI: 10.1038/nrc2621

98. J. M. Lopez-Novoa and M. A. Nieto: Inflammation and EMT: an alliance towards organ fibrosis and cancer progression. EMBO Mol Med, 1(6-7), 303-14 (2009)
DOI: 10.1002/emmm.200900043

99. A. Orimo, P. B. Gupta, D. C. Sgroi, F. Arenzana-Seisdedos, T. Delaunay, R. Naeem, V. J. Carey, A. L. Richardson and R. A. Weinberg: Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell, 121(3), 335-48 (2005)
DOI: 10.1016/j.cell.2005.02.034

100. E. Giannoni, F. Bianchini, L. Calorini and P. Chiarugi: Cancer associated fibroblasts exploit reactive oxygen species through a proinflammatory signature leading to epithelial mesenchymal transition and stemness. Antioxid Redox Signal, 14(12), 2361-71 (2011)
DOI: 10.1089/ars.2010.3727

101. Z. Ao, S. H. Shah, L. M. Machlin, R. Parajuli, P. C. Miller, S. Rawal, A. J. Williams, R. J. Cote, M. E. Lippman, R. H. Datar and D. El-Ashry: Identification of Cancer-Associated Fibroblasts in Circulating Blood from Patients with Metastatic Breast Cancer. Cancer Res, 75(22), 4681-7 (2015)
DOI: 10.1158/0008-5472.CAN-15-1633

102. E. A Ebbing, A. P. van der Zalm, A. Steins, A. Creemers, S.Hermsen, R.Rentenaar,M.Klein, C.Waasdorp, G. K. J.Hooijer, S. L. Meijer, K. K. Krishnadath,C. J. A. Punt, M. I van Berge Henegouwen,.S. S.Gisbertz, O. M. van Delden, Mccm Hulshof, J. P. Medema, H. W. M. van Laarhoven and M. F. Bijlsma. Stromal-derived interleukin 6 drives epithelial-to-mesenchymal transition and therapy resistance in esophageal adenocarcinoma PNAS 116 (6), 2237-2242 (2019).
DOI: 10.1073/pnas.1820459116

103. B. Toh, X. Wang, J. Keeble, W. J. Sim, K. Khoo, W. C. Wong, M. Kato, A. Prevost-Blondel, J. P. Thiery and J. P. Abastado: Mesenchymal transition and dissemination of cancer cells is driven by myeloid-derived suppressor cells infiltrating the primary tumor. PLoS Biol, 9(9), e1001162 (2011)
DOI: 10.1371/journal.pbio.1001162

104. S. Su, Q. Liu, J. Chen, J. Chen, F. Chen, C. He, D. Huang, W. Wu, L. Lin, W. Huang, J. Zhang, X. Cui, F. Zheng, H. Li, H. Yao, F. Su and E. Song: A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell, 25(5), 605-20 (2014)
DOI: 10.1016/j.ccr.2014.03.021

105. V. G. Cooke, V. S. LeBleu, D. Keskin, Z. Khan, J. T. O'Connell, Y. Teng, M. B. Duncan, L. Xie, G. Maeda, S. Vong, H. Sugimoto, R. M. Rocha, A. Damascena, R. R. Brentani and R. Kalluri: Pericyte depletion results in hypoxia-associated epithelial-to-mesenchymal transition and metastasis mediated by met signaling pathway. Cancer Cell, 21(1), 66-81 (2012)
DOI: 10.1016/j.ccr.2011.11.024

106. C. Kudo-Saito, H. Shirako, T. Takeuchi and Y. Kawakami: Cancer metastasis is accelerated through immunosuppression during Snail-induced EMT of cancer cells. Cancer Cell, 15(3), 195-206 (2009)
DOI: 10.1016/j.ccr.2009.01.023

107. L. Y. Ye, W. Chen, X. L. Bai, X. Y. Xu, Q. Zhang, X. F. Xia, X. Sun, G. G. Li, Q. D. Hu, Q. H. Fu and T. B. Liang: Hypoxia-Induced Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma Induces an Immunosuppressive Tumor Microenvironment to Promote Metastasis. Cancer Res, 76(4), 818-30 (2016)
DOI: 10.1158/0008-5472.CAN-15-0977

108. M. Z. Noman, G. Desantis, B. Janji, M. Hasmim, S. Karray, P. Dessen, V. Bronte and S. Chouaib: PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med, 211(5), 781-90 (2014)
DOI: 10.1084/jem.20131916

109. I. Akalay, T. Z. Tan, P. Kumar, B. Janji, F. Mami-Chouaib, C. Charpy, P. Vielh, A. K. Larsen, J. P. Thiery, M. Sabbah and S. Chouaib: Targeting WNT1-inducible signaling pathway protein 2 alters human breast cancer cell susceptibility to specific lysis through regulation of KLF-4 and miR-7 expression. Oncogene, 34(17), 2261-71 (2015)
DOI: 10.1038/onc.2014.151

110. J. M. Hsu, W. Xia, Y. H. Hsu, L. C. Chan, W. H. Yu, J. H. Cha, C. T. Chen, H. W. Liao, C. W. Kuo, K. H. Khoo, J. L. Hsu, C. W. Li, S. O. Lim, S. S. Chang, Y. C. Chen, G. X. Ren and M. C. Hung: STT3-dependent PD-L1 accumulation on cancer stem cells promotes immune evasion. Nat Commun, 9(1), 1908 (2018)
DOI: 10.1038/s41467-018-04313-6

111. M. Z. Noman, B. Janji, A. Abdou, M. Hasmim, S. Terry, T. Z. Tan, F. Mami-Chouaib, J. P. Thiery and S. Chouaib: The immune checkpoint ligand PD-L1 is upregulated in EMT-activated human breast cancer cells by a mechanism involving ZEB-1 and miR-200. Oncoimmunology, 6(1), e1263412 (2017)
DOI: 10.1080/2162402X.2016.1263412

112. A. Dongre, M. Rashidian, F. Reinhardt, A. Bagnato, Z. Keckesova, H. L. Ploegh and R. A. Weinberg: Epithelial-to-Mesenchymal Transition Contributes to Immunosuppression in Breast Carcinomas. Cancer Res, 77(15), 3982-3989 (2017)
DOI: 10.1158/0008-5472.CAN-16-3292

113. Y. Lou, L. Diao, E. R. Cuentas, W. L. Denning, L. Chen, Y. H. Fan, L. A. Byers, J. Wang, V. A. Papadimitrakopoulou, C. Behrens, J. C. Rodriguez, P. Hwu, Wistuba, II, J. V. Heymach and D. L. Gibbons: Epithelial-Mesenchymal Transition Is Associated with a Distinct Tumor Microenvironment Including Elevation of Inflammatory Signals and Multiple Immune Checkpoints in Lung Adenocarcinoma. Clin Cancer Res, 22(14), 3630-42 (2016)
DOI: 10.1158/1078-0432.CCR-15-1434

114. I. J. Fidler: The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nat Rev Cancer, 3(6), 453-8 (2003)
DOI: 10.1038/nrc1098

115. G. P. Gupta and J. Massague: Cancer metastasis: building a framework. Cell, 127(4), 679-95 (2006)
DOI: 10.1016/j.cell.2006.11.001

116. J. E. Talmadge and I. J. Fidler: AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res, 70(14), 5649-69 (2010)
DOI: 10.1158/0008-5472.CAN-10-1040

117. S. Heerboth, G. Housman, M. Leary, M. Longacre, S. Byler, K. Lapinska, A. Willbanks and S. Sarkar: EMT and tumor metastasis. Clin Transl Med, 4, 6 (2015)
DOI: 10.1186/s40169-015-0048-3

118. A. W. Lambert, D. R. Pattabiraman and R. A. Weinberg: Emerging Biological Principles of Metastasis. Cell, 168(4), 670-691 (2017)
DOI: 10.1016/j.cell.2016.11.037

119. Y. Kang and J. Massague: Epithelial-mesenchymal transitions: twist in development and metastasis. Cell, 118(3), 277-9 (2004)
DOI: 10.1016/j.cell.2004.07.011

120. W. Wick, M. Platten and M. Weller: Glioma cell invasion: regulation of metalloproteinase activity by TGF-beta. J Neurooncol, 53(2), 177-85 (2001)

121. W. Wick, C. Wild-Bode, B. Frank and M. Weller: BCL-2-induced glioma cell invasiveness depends on furin-like proteases. J Neurochem, 91(6), 1275-83 (2004)
DOI: 10.1111/j.1471-4159.2004.02806.x

122. B. De Craene and G. Berx: Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer, 13(2), 97-110 (2013)
DOI: 10.1038/nrc3447

123. T. Brabletz: EMT and MET in metastasis: where are the cancer stem cells? Cancer Cell, 22(6), 699-701 (2012)
DOI: 10.1016/j.ccr.2012.11.009

124. T. Brabletz, F. Hlubek, S. Spaderna, O. Schmalhofer, E. Hiendlmeyer, A. Jung and T. Kirchner: Invasion and metastasis in colorectal cancer: epithelial-mesenchymal transition, mesenchymal-epithelial transition, stem cells and beta-catenin. Cells Tissues Organs, 179(1-2), 56-65 (2005)
DOI: 10.1159/000084509

125. M. Korpal, B. J. Ell, F. M. Buffa, T. Ibrahim, M. A. Blanco, T. Celia-Terrassa, L. Mercatali, Z. Khan, H. Goodarzi, Y. Hua, Y. Wei, G. Hu, B. A. Garcia, J. Ragoussis, D. Amadori, A. L. Harris and Y. Kang: Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med, 17(9), 1101-8 (2011)
DOI: 10.1038/nm.2401

126. M. Stankic, S. Pavlovic, Y. Chin, E. Brogi, D. Padua, L. Norton, J. Massague and R. Benezra: TGF-beta-Id1 signaling opposes Twist1 and promotes metastatic colonization via a mesenchymal-to-epithelial transition. Cell Rep, 5(5), 1228-42 (2013)
DOI: 10.1016/j.celrep.2013.11.014

127. J. H. Tsai, J. L. Donaher, D. A. Murphy, S. Chau and J. Yang: Spatiotemporal regulation of epithelial-mesenchymal transition is essential for squamous cell carcinoma metastasis. Cancer Cell, 22(6), 725-36 (2012)
DOI: 10.1016/j.ccr.2012.09.022

128. A. Cano, M. A. Perez-Moreno, I. Rodrigo, A. Locascio, M. J. Blanco, M. G. del Barrio, F. Portillo and M. A. Nieto: The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression. Nat Cell Biol, 2(2), 76-83 (2000)
DOI: 10.1038/35000025

129. D. Medici, E. D. Hay and B. R. Olsen: Snail and Slug promote epithelial-mesenchymal transition through beta-catenin-T-cell factor-4-dependent expression of transforming growth factor-beta3. Mol Biol Cell, 19(11), 4875-87 (2008)
DOI: 10.1091/mbc.E08-05-0506

130. S. Spaderna, O. Schmalhofer, M. Wahlbuhl, A. Dimmler, K. Bauer, A. Sultan, F. Hlubek, A. Jung, D. Strand, A. Eger, T. Kirchner, J. Behrens and T. Brabletz: The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer. Cancer Res, 68(2), 537-44 (2008)
DOI: 10.1158/0008-5472.CAN-07-5682

131. H. D. Tran, K. Luitel, M. Kim, K. Zhang, G. D. Longmore and D. D. Tran: Transient SNAIL1 expression is necessary for metastatic competence in breast cancer. Cancer Res, 74(21), 6330-40 (2014)
DOI: 10.1158/0008-5472.CAN-14-0923

132. A. M. Krebs, J. Mitschke, M. Lasierra Losada, O. Schmalhofer, M. Boerries, H. Busch, M. Boettcher, D. Mougiakakos, W. Reichardt, P. Bronsert, V. G. Brunton, C. Pilarsky, T. H. Winkler, S. Brabletz, M. P. Stemmler and T. Brabletz: The EMT-activator Zeb1 is a key factor for cell plasticity and promotes metastasis in pancreatic cancer. Nat Cell Biol, 19(5), 518-529 (2017)
DOI: 10.1038/ncb3513

133. M. J Alvarez Cubero,. J. A. Lorente, , I. Robles-Fernandez, A. Rodriguez-Martinez, J. L.Puche and M. J. Serrano. Circulating Tumor Cells: Markers and Methodologies for Enrichment and Detection Methods. Mol Biol 1634, 283-303( 2017) 10.1007/978-1-4939-7144-2_24.

134. W. C. Chou, M. H. Wu, P. H. Chang, H. C. Hsu, G. J. Chang, W. K. Huang, C. E. Wu and J. C. Hsieh: A Prognostic Model Based on Circulating Tumour Cells is Useful for Identifying the Poorest Survival Outcome in Patients with Metastatic Colorectal Cancer. Int J Biol Sci, 14(2), 137-146 (2018)
DOI: 10.7150/ijbs.23182

135. M. Cristofanilli, G. T. Budd, M. J. Ellis, A. Stopeck, J. Matera, M. C. Miller, J. M. Reuben, G. V. Doyle, W. J. Allard, L. W. Terstappen and D. F. Hayes: Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med, 351(8), 781-91 (2004)
DOI: 10.1056/NEJMoa040766

136. L. Resel Folkersma, L. San Jose Manso, I. Galante Romo, J. Moreno Sierra and C. Olivier Gomez: Prognostic significance of circulating tumor cell count in patients with metastatic hormone-sensitive prostate cancer. Urology, 80(6), 1328-32 (2012)
DOI: 10.1016/j.urology.2012.09.001

137. B. Tong, Y. Xu, J. Zhao, M. Chen, J. Xing, W. Zhong and M. Wang: Prognostic significance of circulating tumor cells in non-small cell lung cancer patients undergoing chemotherapy. Oncotarget, 8(49), 86615-86624 (2017)
DOI: 10.18632/oncotarget.21255

138. D. L. Adams, D. K. Adams, S. Stefansson, C. Haudenschild, S. S. Martin, M. Charpentier, S. Chumsri, M. Cristofanilli, C. M. Tang and R. K. Alpaugh: Mitosis in circulating tumor cells stratifies highly aggressive breast carcinomas. Breast Cancer Res, 18(1), 44 (2016)
DOI: 10.1186/s13058-016-0706-4

139. D. S. Micalizzi, D. A. Haber and S. Maheswaran: Cancer metastasis through the prism of epithelial-to-mesenchymal transition in circulating tumor cells. Mol Oncol, 11(7), 770-780 (2017)
DOI: 10.1002/1878-0261.12081

140. H. W. Hou, M. E. Warkiani, B. L. Khoo, Z. R. Li, R. A. Soo, D. S. Tan, W. T. Lim, J. Han, A. A. Bhagat and C. T. Lim: Isolation and retrieval of circulating tumor cells using centrifugal forces. Sci Rep, 3, 1259 (2013)
DOI: 10.1038/srep01259

141. S. Wu, S. Liu, Z. Liu, J. Huang, X. Pu, J. Li, D. Yang, H. Deng, N. Yang and J. Xu: Classification of circulating tumor cells by epithelial-mesenchymal transition markers. PLoS One, 10(4), e0123976 (2015)
DOI: 10.1371/journal.pone.0123976

142. J. Shaw Bagnall, S. Byun, D. T. Miyamoto, J. H. Kang, S. Maheswaran, S. L. Stott, M. Toner and S. R. Manalis: Deformability-based cell selection with downstream immunofluorescence analysis. Integr Biol (Camb), 8(5), 654-64 (2016)
DOI: 10.1039/c5ib00284b

143. S. Nagrath, L. V. Sequist, S. Maheswaran, D. W. Bell, D. Irimia, L. Ulkus, M. R. Smith, E. L. Kwak, S. Digumarthy, A. Muzikansky, P. Ryan, U. J. Balis, R. G. Tompkins, D. A. Haber and M. Toner: Isolation of rare circulating tumour cells in cancer patients by microchip technology. Nature, 450(7173), 1235-9 (2007)
DOI: 10.1038/nature06385

144. E. Ozkumur, A. M. Shah, J. C. Ciciliano, B. L. Emmink, D. T. Miyamoto, E. Brachtel, M. Yu, P. I. Chen, B. Morgan, J. Trautwein, A. Kimura, S. Sengupta, S. L. Stott, N. M. Karabacak, T. A. Barber, J. R. Walsh, K. Smith, P. S. Spuhler, J. P. Sullivan, R. J. Lee, D. T. Ting, X. Luo, A. T. Shaw, A. Bardia, L. V. Sequist, D. N. Louis, S. Maheswaran, R. Kapur, D. A. Haber and M. Toner: Inertial focusing for tumor antigen-dependent and -independent sorting of rare circulating tumor cells. Sci Transl Med, 5(179), 179ra47 (2013)
DOI: 10.1126/scitranslmed.3005616

145. H. Schneck, B. Gierke, F. Uppenkamp, B. Behrens, D. Niederacher, N. H. Stoecklein, M. F. Templin, M. Pawlak, T. Fehm, H. Neubauer and D. Disseminated Cancer Cell Network: EpCAM-Independent Enrichment of Circulating Tumor Cells in Metastatic Breast Cancer. PLoS One, 10(12), e0144535 (2015)
DOI: 10.1371/journal.pone.0144535

146. N. Aceto, A. Bardia, D. T. Miyamoto, M. C. Donaldson, B. S. Wittner, J. A. Spencer, M. Yu, A. Pely, A. Engstrom, H. Zhu, B. W. Brannigan, R. Kapur, S. L. Stott, T. Shioda, S. Ramaswamy, D. T. Ting, C. P. Lin, M. Toner, D. A. Haber and S. Maheswaran: Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis. Cell, 158(5), 1110-1122 (2014)
DOI: 10.1016/j.cell.2014.07.013

147. W. Li and Y. Kang: Probing the Fifty Shades of EMT in Metastasis. Trends Cancer, 2(2), 65-67 (2016)
DOI: 10.1016/j.trecan.2016.01.001

148. A. Grosse-Wilde, A. Fouquier d'Herouel, E. McIntosh, G. Ertaylan, A. Skupin, R. E. Kuestner, A. del Sol, K. A. Walters and S. Huang: Stemness of the hybrid Epithelial/Mesenchymal State in Breast Cancer and Its Association with Poor Survival. PLoS One, 10(5), e0126522 (2015)
DOI: 10.1371/journal.pone.0126522

149. W. L. Tam and R. A. Weinberg: The epigenetics of epithelial-mesenchymal plasticity in cancer. Nat Med, 19(11), 1438-49 (2013)
DOI: 10.1038/nm.3336

150. M. J. Schliekelman, A. Taguchi, J. Zhu, X. Dai, J. Rodriguez, M. Celiktas, Q. Zhang, A. Chin, C. H. Wong, H. Wang, L. McFerrin, S. A. Selamat, C. Yang, E. M. Kroh, K. S. Garg, C. Behrens, A. F. Gazdar, I. A. Laird-Offringa, M. Tewari, Wistuba, II, J. P. Thiery and S. M. Hanash: Molecular portraits of epithelial, mesenchymal, and hybrid States in lung adenocarcinoma and their relevance to survival. Cancer Res, 75(9), 1789-800 (2015)
DOI: 10.1158/0008-5472.CAN-14-2535

151. A. J. Armstrong, M. S. Marengo, S. Oltean, G. Kemeny, R. L. Bitting, J. D. Turnbull, C. I. Herold, P. K. Marcom, D. J. George and M. A. Garcia-Blanco: Circulating tumor cells from patients with advanced prostate and breast cancer display both epithelial and mesenchymal markers. Mol Cancer Res, 9(8), 997-1007 (2011)
DOI: 10.1158/1541-7786.MCR-10-0490

152. M. K. Jolly, J. A. Somarelli, M. Sheth, A. Biddle, S. C. Tripathi, A. J. Armstrong, S. M. Hanash, S. A. Bapat, A. Rangarajan and H. Levine: Hybrid epithelial/mesenchymal phenotypes promote metastasis and therapy resistance across carcinomas. Pharmacol Ther, 194, 161-184 (2019)
DOI: 10.1016/j.pharmthera.2018.09.007

153. N. M. Aiello, R. Maddipati, R. J. Norgard, D. Balli, J. Li, S. Yuan, T. Yamazoe, T. Black, A. Sahmoud, E. E. Furth, D. Bar-Sagi and B. Z. Stanger: EMT Subtype Influences Epithelial Plasticity and Mode of Cell Migration. Dev Cell, 45(6), 681-695 e4 (2018)
DOI: 10.1016/j.devcel.2018.05.027

154. A. Lecharpentier, P. Vielh, P. Perez-Moreno, D. Planchard, J. C. Soria and F. Farace: Detection of circulating tumour cells with a hybrid (epithelial/mesenchymal) phenotype in patients with metastatic non-small cell lung cancer. Br J Cancer, 105(9), 1338-41 (2011)
DOI: 10.1038/bjc.2011.405

155. S. H. Au, B. D. Storey, J. C. Moore, Q. Tang, Y. L. Chen, S. Javaid, A. F. Sarioglu, R. Sullivan, M. W. Madden, R. O'Keefe, D. A. Haber, S. Maheswaran, D. M. Langenau, S. L. Stott and M. Toner: Clusters of circulating tumor cells traverse capillary-sized vessels. Proc Natl Acad Sci U S A, 113(18), 4947-52 (2016)
DOI: 10.1073/pnas.1524448113

156. X. J. Tian, H. Zhang and J. Xing: Coupled reversible and irreversible bistable switches underlying TGFbeta-induced epithelial to mesenchymal transition. Biophys J, 105(4), 1079-89 (2013)
DOI: 10.1016/j.bpj.2013.07.011

157. J. Zhang, X. J. Tian, H. Zhang, Y. Teng, R. Li, F. Bai, S. Elankumaran and J. Xing: TGF-beta-induced epithelial-to-mesenchymal transition proceeds through stepwise activation of multiple feedback loops. Sci Signal, 7(345), ra91 (2014)
DOI: 10.1126/scisignal.2005304

158. T. Hong, K. Watanabe, C. H. Ta, A. Villarreal-Ponce, Q. Nie and X. Dai: An Ovol2-Zeb1 Mutual Inhibitory Circuit Governs Bidirectional and Multi-step Transition between Epithelial and Mesenchymal States. PLoS Comput Biol, 11(11), e1004569 (2015)
DOI: 10.1371/journal.pcbi.1004569

159. M. K. Jolly, S. C. Tripathi, D. Jia, S. M. Mooney, M. Celiktas, S. M. Hanash, S. A. Mani, K. J. Pienta, E. Ben-Jacob and H. Levine: Stability of the hybrid epithelial/mesenchymal phenotype. Oncotarget, 7(19), 27067-84 (2016)
DOI: 10.18632/oncotarget.8166

160. M. Diepenbruck and G. Christofori: Epithelial-mesenchymal transition (EMT) and metastasis: yes, no, maybe? Curr Opin Cell Biol, 43, 7-13 (2016)
DOI: 10.1016/j.ceb.2016.06.002

161. H. Jung, L. Fattet and J. Yang. Molecular Pathways: Linking Tumor Microenvironment to Epithelial–Mesenchymal Transition in Metastasis. Clin. Cancer Res. 21(5),962-968 (2015) doi.10.1158/1078-0432.CCR-13-3173

162. S. Valastyan and R. A. Weinberg: Tumor metastasis: molecular insights and evolving paradigms. Cell, 147(2), 275-92 (2011)
DOI: 10.1016/j.cell.2011.09.024

163. S. Meng, D. Tripathy, E. P. Frenkel, S. Shete, E. Z. Naftalis, J. F. Huth, P. D. Beitsch, M. Leitch, S. Hoover, D. Euhus, B. Haley, L. Morrison, T. P. Fleming, D. Herlyn, L. W. Terstappen, T. Fehm, T. F. Tucker, N. Lane, J. Wang and J. W. Uhr: Circulating tumor cells in patients with breast cancer dormancy. Clin Cancer Res, 10(24), 8152-62 (2004)
DOI: 10.1158/1078-0432.CCR-04-1110

164. A. Kowalik, M. Kowalewska and S. Gozdz: Current approaches for avoiding the limitations of circulating tumor cells detection methods-implications for diagnosis and treatment of patients with solid tumors. Transl Res, 185, 58-84 e15 (2017)
DOI: 10.1016/j.trsl.2017.04.002

165. M. Labelle, S. Begum and R. O. Hynes: Direct signaling between platelets and cancer cells induces an epithelial-mesenchymal-like transition and promotes metastasis. Cancer Cell, 20(5), 576-90 (2011)
DOI: 10.1016/j.ccr.2011.09.009

166. R. Leblanc, S. C. Lee, M. David, J. C. Bordet, D. D. Norman, R. Patil, D. Miller, D. Sahay, J. Ribeiro, P. Clezardin, G. J. Tigyi and O. Peyruchaud: Interaction of platelet-derived autotaxin with tumor integrin alphaVbeta3 controls metastasis of breast cancer cells to bone. Blood, 124(20), 3141-50 (2014)
DOI: 10.1182/blood-2014-04-568683

167. L. X. Yu, L. Yan, W. Yang, F. Q. Wu, Y. Ling, S. Z. Chen, L. Tang, Y. X. Tan, D. Cao, M. C. Wu, H. X. Yan and H. Y. Wang: Platelets promote tumour metastasis via interaction between TLR4 and tumour cell-released high-mobility group box1 protein. Nat Commun, 5, 5256 (2014)
DOI: 10.1038/ncomms6256

168. S. Takagi, S. Sato, T. Oh-hara, M. Takami, S. Koike, Y. Mishima, K. Hatake and N. Fujita: Platelets promote tumor growth and metastasis via direct interaction between Aggrus/podoplanin and CLEC-2. PLoS One, 8(8), e73609 (2013)
DOI: 10.1371/journal.pone.0073609

169. C. Alix-Panabieres and K. PanTel: Challenges in circulating tumour cell research. Nat Rev Cancer, 14(9), 623-31 (2014)
DOI: 10.1038/nrc3820

170. T. Z. Tan, Q. H. Miow, Y. Miki, T. Noda, S. Mori, R. Y. Huang and J. P. Thiery: Epithelial-mesenchymal transition spectrum quantification and its efficacy in deciphering survival and drug responses of cancer patients. EMBO Mol Med, 6(10), 1279-93 (2014)
DOI: 10.15252/emmm.201404208

171. A. Markiewicz and A. J. Zaczek: The Landscape of Circulating Tumor Cell Research in the Context of Epithelial-Mesenchymal Transition. Pathobiology, 84(5), 264-283 (2017)
DOI: 10.1159/000477812

172. T. Yokobori, H. Iinuma, T. Shimamura, S. Imoto, K. Sugimachi, H. Ishii, M. Iwatsuki, D. Ota, M. Ohkuma, T. Iwaya, N. Nishida, R. Kogo, T. Sudo, F. Tanaka, K. Shibata, H. Toh, T. Sato, G. F. Barnard, T. Fukagawa, S. Yamamoto, H. Nakanishi, S. Sasaki, S. Miyano, T. Watanabe, H. Kuwano, K. Mimori, K. Pantel and M. Mori: Plastin3 is a novel marker for circulating tumor cells undergoing the epithelial-mesenchymal transition and is associated with colorectal cancer prognosis. Cancer Res, 73(7), 2059-69 (2013)
DOI: 10.1158/0008-5472.CAN-12-0326

173. H. Ueo, K. Sugimachi, T. M. Gorges, K. Bartkowiak, T. Yokobori, V. Muller, Y. Shinden, M. Ueda, H. Ueo, M. Mori, H. Kuwano, Y. Maehara, S. Ohno, K. Pantel and K. Mimori: Circulating tumour cell-derived plastin3 is a novel marker for predicting long-term prognosis in patients with breast cancer. Br J Cancer, 112(9), 1519-26 (2015)
DOI: 10.1038/bjc.2015.132

174. W. Goto, S. Kashiwagi, Y. Asano, K. Takada, K. Takahashi, T. Hatano, T. Takashima, S. Tomita, H. Motomura, M. Ohsawa, K. Hirakawa and M. Ohira: Circulating tumor cell clusters-associated gene plakoglobin is a significant prognostic predictor in patients with breast cancer. Biomark Res, 5, 19 (2017)
DOI: 10.1186/s40364-017-0099-2

175. A. S. Ribeiro and J. Paredes: P-Cadherin Linking Breast Cancer Stem Cells and Invasion: A Promising Marker to Identify an "Intermediate/Metastable" EMT State. Front Oncol, 4, 371 (2014)
DOI: 10.3389/fonc.2014.00371

176. S. Yadavalli, S. Jayaram, S. S. Manda, A. K. Madugundu, D. S. Nayakanti, T. Z. Tan, R. Bhat, A. Rangarajan, A. Chatterjee, H. Gowda, J. P. Thiery and P. Kumar: Data-Driven Discovery of Extravasation Pathway in Circulating Tumor Cells. Sci Rep, 7, 43710 (2017)
DOI: 10.1038/srep43710

177. C. Alix-Panabieres, H. Schwarzenbach and K. PanTel: Circulating tumor cells and circulating tumor DNA. Annu Rev Med, 63, 199-215 (2012)
DOI: 10.1146/annurev-med-062310-094219

178. Y. Kang and K. PanTel: Tumor cell dissemination: emerging biological insights from animal models and cancer patients. Cancer Cell, 23(5), 573-81 (2013)
DOI: 10.1016/j.ccr.2013.04.017

179. S. L. Kong, X. Liu, N. M. Suhaimi, K. J. H. Koh, M. Hu, D. Y. S. Lee, I. Cima, W. M. Phyo, E. X. W. Lee, J. A. Tai, Y. M. Foong, J. H. Vo, P. K. Koh, T. Zhang, J. Y. Ying, B. Lim, M. H. Tan and A. M. Hillmer: Molecular characterization of circulating colorectal tumor cells defines genetic signatures for individualized cancer care. Oncotarget, 8(40), 68026-68037 (2017)
DOI: 10.18632/oncotarget.19138

180. B. L. Khoo, S. C. Lee, P. Kumar, T. Z. Tan, M. E. Warkiani, S. G. Ow, S. Nandi, C. T. Lim and J. P. Thiery: Short-term expansion of breast circulating cancer cells predicts response to anti-cancer therapy. Oncotarget, 6(17), 15578-93 (2015)
DOI: 10.18632/oncotarget.3903

181. R. Zhao, Z. Cai, S. Li, Y. Cheng, H. Gao, F. Liu, S. Wu, S. Liu, Y. Dong, L. Zheng, W. Zhang, X. Wu and X. Yao: Expression and clinical relevance of epithelial and mesenchymal markers in circulating tumor cells from colorectal cancer. Oncotarget, 8(6), 9293-9302 (2017)
DOI: 10.18632/oncotarget.14065

182. A. Satelli, I. S. Batth, Z. Brownlee, C. Rojas, Q. H. Meng, S. Kopetz and S. Li: Potential role of nuclear PD-L1 expression in cell-surface vimentin positive circulating tumor cells as a prognostic marker in cancer patients. Sci Rep, 6, 28910 (2016)
DOI: 10.1038/srep28910

183. M. Yu, A. Bardia, N. Aceto, F. Bersani, M. W. Madden, M. C. Donaldson, R. Desai, H. Zhu, V. Comaills, Z. Zheng, B. S. Wittner, P. Stojanov, E. Brachtel, D. Sgroi, R. Kapur, T. Shioda, D. T. Ting, S. Ramaswamy, G. Getz, A. J. Iafrate, C. Benes, M. Toner, S. Maheswaran and D. A. Haber: Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility. Science, 345(6193), 216-20 (2014)
DOI: 10.1126/science.1253533

184. A. F. Sarioglu, N. Aceto, N. Kojic, M. C. Donaldson, M. Zeinali, B. Hamza, A. Engstrom, H. Zhu, T. K. Sundaresan, D. T. Miyamoto, X. Luo, A. Bardia, B. S. Wittner, S. Ramaswamy, T. Shioda, D. T. Ting, S. L. Stott, R. Kapur, S. Maheswaran, D. A. Haber and M. Toner: A microfluidic device for label-free, physical capture of circulating tumor cell clusters. Nat Methods, 12(7), 685-91 (2015)
DOI: 10.1038/nmeth.3404

185. R. Divella, A. Daniele, I. Abbate, A. Bellizzi, E. Savino, G. Simone, G. Giannone, F. Giuliani, V. Fazio, G. Gadaleta-Caldarola, C. D. Gadaleta, I. Lolli, C. Sabba and A. Mazzocca: The presence of clustered circulating tumor cells (CTCs) and circulating cytokines define an aggressive phenotype in metastatic colorectal cancer. Cancer Causes Control, 25(11), 1531-41 (2014)
DOI: 10.1007/s10552-014-0457-4

186. C. Wang, Z. Mu, I. Chervoneva, L. Austin, Z. Ye, G. Rossi, J. P. Palazzo, C. Sun, M. Abu-Khalaf, R. E. Myers, Z. Zhu, Y. Ba, B. Li, L. Hou, M. Cristofanilli and H. Yang: Longitudinally collected CTCs and CTC-clusters and clinical outcomes of metastatic breast cancer. Breast Cancer Res Treat, 161(1), 83-94 (2017)
DOI: 10.1007/s10549-016-4026-2

187. A. Josefsson, A. Linder, D. Flondell Site, G. Canesin, A. Stiehm, A. Anand, A. Bjartell, J. E. Damber and K. Welen: Circulating Tumor Cells as a Marker for Progression-free Survival in Metastatic Castration-naive Prostate Cancer. Prostate, 77(8), 849-858 (2017)
DOI: 10.1002/pros.23325

188. C. H. Wang, C. J. Chang, K. Y. Yeh, P. H. Chang and J. S. Huang: The Prognostic Value of HER2-Positive Circulating Tumor Cells in Breast Cancer Patients: A Systematic Review and Meta-Analysis. Clin Breast Cancer, 17(5), 341-349 (2017)
DOI: 10.1016/j.clbc.2017.02.002

189. A. Satelli, A. Mitra, Z. Brownlee, X. Xia, S. Bellister, M. J. Overman, S. Kopetz, L. M. Ellis, Q. H. Meng and S. Li: Epithelial-mesenchymal transitioned circulating tumor cells capture for detecting tumor progression. Clin Cancer Res, 21(4), 899-906 (2015)
DOI: 10.1158/1078-0432.CCR-14-0894

190. B. Aktas, M. Tewes, T. Fehm, S. Hauch, R. Kimmig and S. Kasimir-Bauer: Stem cell and epithelial-mesenchymal transition markers are frequently overexpressed in circulating tumor cells of metastatic breast cancer patients. Breast Cancer Res, 11(4), R46 (2009)
DOI: 10.1186/bcr2333

191. K. E. Poruk, A. L. Blackford, M. J. Weiss, J. L. Cameron, J. He, M. Goggins, Z. A. Rasheed, C. L. Wolfgang and L. D. Wood: Circulating Tumor Cells Expressing Markers of Tumor-Initiating Cells Predict Poor Survival and Cancer Recurrence in Patients with Pancreatic Ductal Adenocarcinoma. Clin Cancer Res, 23(11), 2681-2690 (2017)
DOI: 10.1158/1078-0432.CCR-16-1467

192. M. A. Papadaki, G. Kallergi, Z. Zafeiriou, L. Manouras, P. A. Theodoropoulos, D. Mavroudis, V. Georgoulias and S. Agelaki: Co-expression of putative stemness and epithelial-to-mesenchymal transition markers on single circulating tumour cells from patients with early and metastatic breast cancer. BMC Cancer, 14, 651 (2014)
DOI: 10.1186/1471-2407-14-651

193. M. Pore, C. Meijer, G. H. de Bock, W. Boersma-van Ek, L. W. Terstappen, H. J. Groen, W. Timens, F. A. Kruyt and T. J. Hiltermann: Cancer Stem Cells, Epithelial to Mesenchymal Markers, and Circulating Tumor Cells in Small Cell Lung Cancer. Clin Lung Cancer, 17(6), 535-542 (2016)
DOI: 10.1016/j.cllc.2016.05.015

194. P. Weller, I. Nel, P. Hassenkamp, T. Gauler, A. Schlueter, S. Lang, P. Dountsop, A. C. Hoffmann and G. Lehnerdt: Detection of circulating tumor cell subpopulations in patients with head and neck squamous cell carcinoma (HNSCC). PLoS One, 9(12), e113706 (2014)
DOI: 10.1371/journal.pone.0113706

195. E. V. Kaigorodova, O. E. Savelieva, L. A. Tashireva, N. A. Tarabanovskaya, E. I. Simolina, E. V. Denisov, E. M. Slonimskaya, E. L. Choynzonov and V. M. Perelmuter: Heterogeneity of Circulating Tumor Cells in Neoadjuvant Chemotherapy of Breast Cancer. Molecules, 23(4) (2018)
DOI: 10.3390/molecules23040727

196. C. R. Lindsay, V. Faugeroux, S. Michiels, E. Pailler, F. Facchinetti, D. Ou, M. V. Bluthgen, C. Pannet, M. Ngo-Camus, G. Bescher, C. Caramella, F. Billiot, J. Remon, D. Planchard, J. C. Soria, B. Besse and F. Farace: A prospective examination of circulating tumor cell profiles in non-small-cell lung cancer molecular subgroups. Ann Oncol, 28(7), 1523-1531 (2017)
DOI: 10.1093/annonc/mdx156

197. X. Guan, F. Ma, C. Li, S. Wu, S. Hu, J. Huang, X. Sun, J. Wang, Y. Luo, R. Cai, Y. Fan, Q. Li, S. Chen, P. Zhang, Q. Li and B. Xu: The prognostic and therapeutic implications of circulating tumor cell phenotype detection based on epithelial-mesenchymal transition markers in the first-line chemotherapy of HER2-negative metastatic breast cancer. Cancer Commun (Lond), 39(1), 1 (2019)
DOI: 10.1186/s40880-018-0346-4

198. A. Markiewicz, M. Ksiazkiewicz, M. Welnicka-Jaskiewicz, B. Seroczynska, J. Skokowski, J. Szade and A. J. Zaczek: Mesenchymal phenotype of CTC-enriched blood fraction and lymph node metastasis formation potential. PLoS One, 9(4), e93901 (2014)
DOI: 10.1371/journal.pone.0093901

199. B. Kulemann, A. S. Liss, A. L. Warshaw, S. Seifert, P. Bronsert, T. Glatz, M. B. Pitman and J. Hoeppner: KRAS mutations in pancreatic circulating tumor cells: a pilot study. Tumour Biol, 37(6), 7547-54 (2016)
DOI: 10.1007/s13277-015-4589-2

200. L. N. Qi, B. D. Xiang, F. X. Wu, J. Z. Ye, J. H. Zhong, Y. Y. Wang, Y. Y. Chen, Z. S. Chen, L. Ma, J. Chen, W. F. Gong, Z. G. Han, Y. Lu, J. J. Shang and L. Q. Li: Circulating Tumor Cells Undergoing EMT Provide a Metric for Diagnosis and Prognosis of Patients with Hepatocellular Carcinoma. Cancer Res, 78(16), 4731-4744 (2018)
DOI: 10.1158/0008-5472.CAN-17-2459

201. I. Chebouti, S. Kasimir-Bauer, P. Buderath, P. Wimberger, S. Hauch, R. Kimmig and J. D. Kuhlmann: EMT-like circulating tumor cells in ovarian cancer patients are enriched by platinum-based chemotherapy. Oncotarget, 8(30), 48820-48831 (2017)
DOI: 10.18632/oncotarget.16179

202. L. A. Devriese, A. J. Bosma, M. M. van de Heuvel, W. Heemsbergen, E. E. Voest and J. H. Schellens: Circulating tumor cell detection in advanced non-small cell lung cancer patients by multi-marker QPCR analysis. Lung Cancer, 75(2), 242-7 (2012)
DOI: 10.1016/j.lungcan.2011.07.003

Key Words: Liquid Biopsy, Neoplasia, Invasion, Hybrid Phenotype, Cadherin Switch, Review

Send correspondence to: Remya Raja, Institute of Bioinformatics, Discover Building, International Tech Park, Bangalore- 560066, India, Tel: 91-80-28416140, Fax: 91-80-28416132. E-mail: remya@ibioinformatics.org