Epigenetic plasticity: A central regulator of epithelial-to-mesenchymal transition in cancer

Upasana Bedi, Vivek Kumar Mishra, David Wasilewski, Christina Scheel and Steven A. Johnsen _

PDF  |  HTML  |  How to cite

Oncotarget. 2014; 5:2016-2029. https://doi.org/10.18632/oncotarget.1875

Metrics: PDF 4151 views  |   HTML 5955 views  |   ?  


Upasana Bedi1,2, Vivek Kumar Mishra2,3, David Wasilewski4, Christina Scheel4, Steven A. Johnsen2,3

1 Department of Molecular Oncology, Göttingen Center for Molecular Biosciences, University Medical Center Göttingen, Göttingen, Germany

2 Department of Tumor Biology, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany

3 Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany

4 Institute of Stem Cell Research, Helmholtz Centre Munich, Munich, Germany


Steven Johnsen, email:

Keywords: Epigenetics, Chromatin, Cancer, Epithelial-to-mesenchymal transition, Metastasis

Received: February 22, 2014 Accepted: March 27, 2014 Published: March 28, 2014


Tumor metastasis is the major cause of mortality and morbidity in most solid cancers. A growing body of evidence suggests that the epithelial-to-mesenchymal transition (EMT) plays a central role during tumor metastasis and frequently imparts a stem cell-like phenotype and therapeutic resistance to tumor cells. The induction of EMT is accompanied by a dynamic reprogramming of the epigenome involving changes in DNA methylation and several post-translational histone modifications. These changes in turn promote the expression of mesenchymal genes or repress those associated with an epithelial phenotype. Importantly, in order for metastatic colonization and the formation of macrometastases to occur, tumor cells frequently undergo a reversal of EMT referred to as the mesenchymal-to-epithelial transition (MET). Thus, a high degree of epigenetic plasticity is required in order to induce and reverse EMT during tumor progression. In this review, we describe various epigenetic regulatory mechanisms employed by tumor cells during EMT and elaborate on the importance of the histone code in controlling both the expression and activity of EMT-associated transcription factors. We propose that a more thorough understanding of the epigenetic mechanisms controlling EMT may provide new opportunities which may be harnessed for improved and individualized cancer therapy based on defined molecular mechanisms.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 1875