[Frontiers in Bioscience S3, 621-631, January 1, 2011]

MTSS1: a multifunctional protein and its role in cancer invasion and metastasis

Fei Xie1, 2, Lin Ye1, Martin TA1, Lijian Zhang2, Wen G. Jiang1

1Metastasis and Angiogenesis Research Group, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK, 2Key laboratory of Carcinogenesis and Translational Research(Ministry of Education, Department of Thoracic Surgery, Peking University School of Oncology and Beijing Cancer Hospital, Beijing, 100142, China

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Cytoskeletal regulation in cancer cell migration
3.1. Membrane protrusions formed by migrating cells
3.2. Signaling pathways involved in cell migration
3.2.1. Rho GTPases
3.2.2. WASP family proteins
3.2.3. Arp2/3 complex
3.2.4. Cortactin
3.2.5. LIMK-1/Cofilin
4. Protein structure of MTSS1 and its splicing variants
4.1. Protein structure
4.2. Splicing variants
5. Function of MTSS1
5.1. MTSS1 acts as a cytoskeletal scaffold protein
5.1.1. Binding and bindling actin filaments
5.1.2. Interaction with the small GTPase Rac
5.1.3. Interaction with cortactin
5.1.4. Interaction with membrane
5.1.5. Interaction with RPTP delta
5.1.6. Plays a role in PDGF signaling pathway
5.2. MTSS1 Acts as a new Shh-responsive gene
6. Expression of MTSS1 in cancer and its clinical significance
6.1. Expression of MTSS1 in cancer
6.2. Methylation may be involved in the regulation of MTSS1 expression
6.3. The clinical significance of MTSS1
7. Perspective
8. Acknowledgements
9. References

1. ABSTRACT

MTSS1 (metastasis suppressor-1) was first identified as a metastasis suppressor missing in metastatic bladder carcinoma cell lines. The down-regulation of MTSS1 that may be caused by DNA methylation was also observed in many other types of cancer. While accumlating evidence for the function of MTSS1 support the concept that it is unlikely to be a metastasis suppressor, but actually acts as a scaffold protein that interacts with multiple partners to regulate actin dynamics. It has also been demonstrated that MTSS1 is involved in the Shh signaling pathway in the developing hair follicle and in basal cell carcinomas of the skin. Such evidence indicates that MTSS1 as a multiple functional molecular player and has an important role in development, carcinogenesis and metastasis. However, the biochemical mechanisms by which MTSS1 functions in cells and the physiological role of this protein in animals remain largely unknown. In this review, we will discuss the current knowledge of MTSS1's role in cancer metastasis, carcinogenesis, and development. The clinical significance of MTSS1 will also be discussed.