[Frontiers in Bioscience 14, 3041-3050, January 1, 2009]

Role of the epithelial-mesenchymal transition regulator Slug in primary human cancers

Catarina Castro Alves1, Fatima Carneiro1, Heinz Hoefler2,3, Karl-Friedrich Becker2

1Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP) Rua Dr. Roberto Frias, S/N 4200-465 Porto, Portugal, 2Institute of Pathology, Technical University of Munich, Trogerstrasse 18, D-81765 Munich, Germany, 3Helmholtz Zentrum Muenchen - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Ingolstaedter Landstraße 1, D-85764 Neuherberg, Germany

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Slug and cancer
3.1. Slug expression in various types of tumors
3.1.1. Breast Cancer
3.1.2. Esophageal Squamous Cell Carcinoma
3.1.3. Gastric Carcinoma
3.1.4. Colorectal Carcinoma
3.1.5. Hepatocellular Carcinoma
3.1.6. Pancreatic cancer
3.1.7. Lung Adenocarcinoma
3.1.8. Malignant Mesothelioma
3.1.9. Ovarian Carcinoma
3.2. Relevant data from in vitro studies
4. Conclusions and perspectives
5. Acknowledgment
6. References

1. ABSTRACT

Epithelial-mesenchymal-transition (EMT) is a crucial process during morphogenesis of multi-cellular organisms. EMT not only is a normal developmental process but also plays a role in tumor invasion and metastasis. Indeed, molecules involved in EMT, such as the transcription factor and E-cadherin repressor Slug (SNAI2), have recently been demonstrated to be important for cancer cells to down-regulate epithelial markers and up-regulate mesenchymal markers in order to become motile and invasive. Here we summarize major studies focusing on Slug expression in human tumor samples. We review a total of 13 studies involving 1150 cases from 9 different types of tumors. It is becoming clear that this transcription factor plays a role in the progression of some tumor types, including breast and gastric cancer. Interestingly, Slug expression is not always associated with down-regulation of E-cadherin. The mode of action, the signaling pathways involved in its regulation, and the interplay with other EMT regulators need to be addressed in future studies in order to fully understand Slug's role in tumor progression.