Epithelial-to-mesenchymal transition in cancer: complexity and opportunities

Abstract

The cell-biological program termed the epithelial-to-mesenchymal transition (EMT) plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenchymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.

Keywords

epithelial-to-mesenchymal transition / cancer / metastasis / cancer stem cell

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Acknowledgements

We would like to thank all members of the R.A.W. laboratory for fruitful discussions and especially Arthur W. Lambert for critical review of the manuscript. We would also like to thank Meredith Leffler for preparation of the figures. Y.Z. is supported by Susan G. Komen Postdoctoral Fellowship (No. PDF15301255). Work in the R.A.W. laboratory is supported by grants from the NIH (No. R01-CA078461), the Breast Cancer Research Foundation, the Advanced Medical Research Foundation, and the Ludwig Center for Molecular Oncology. R.A.W. is an American Cancer Society Research Professor and a Daniel K. Ludwig Cancer Research Professor.

Compliance with ethics guidelines

Yun Zhang and Robert A. Weinberg declare no competing interests. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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2018 The Author(s) 2018. This article is published with open access at link.springer.com and journal.hep.com.cn