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

Upasana Bedi, Vivek Kumar Mishra, David Wasilewski, Christina Scheel, Steven Johnsen

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

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 EMTassociated 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.

Original languageEnglish (US)
Pages (from-to)2016-2029
Number of pages14
JournalOncotarget
Volume5
Issue number8
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

Epithelial-Mesenchymal Transition
Epigenomics
Neoplasms
Histone Code
Neoplasm Metastasis
Phenotype
DNA Methylation
Post Translational Protein Processing
Transcription Factors
Stem Cells
Morbidity
Gene Expression
Mortality
Therapeutics

Keywords

  • Cancer
  • Chromatin
  • Epigenetics
  • Epithelial-to-mesenchymal transition
  • Metastasis

ASJC Scopus subject areas

  • Oncology

Cite this

Epigenetic plasticity : A central regulator of epithelial-tomesenchymal transition in cancer. / Bedi, Upasana; Mishra, Vivek Kumar; Wasilewski, David; Scheel, Christina; Johnsen, Steven.

In: Oncotarget, Vol. 5, No. 8, 01.01.2014, p. 2016-2029.

Research output: Contribution to journalArticle

Bedi, Upasana ; Mishra, Vivek Kumar ; Wasilewski, David ; Scheel, Christina ; Johnsen, Steven. / Epigenetic plasticity : A central regulator of epithelial-tomesenchymal transition in cancer. In: Oncotarget. 2014 ; Vol. 5, No. 8. pp. 2016-2029.
@article{7215a064901a4667850956374900daff,
title = "Epigenetic plasticity: A central regulator of epithelial-tomesenchymal transition in cancer",
abstract = "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 EMTassociated 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.",
keywords = "Cancer, Chromatin, Epigenetics, Epithelial-to-mesenchymal transition, Metastasis",
author = "Upasana Bedi and Mishra, {Vivek Kumar} and David Wasilewski and Christina Scheel and Steven Johnsen",
year = "2014",
month = "1",
day = "1",
doi = "10.18632/oncotarget.1875",
language = "English (US)",
volume = "5",
pages = "2016--2029",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "8",

}

TY - JOUR

T1 - Epigenetic plasticity

T2 - A central regulator of epithelial-tomesenchymal transition in cancer

AU - Bedi, Upasana

AU - Mishra, Vivek Kumar

AU - Wasilewski, David

AU - Scheel, Christina

AU - Johnsen, Steven

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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 EMTassociated 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.

AB - 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 EMTassociated 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.

KW - Cancer

KW - Chromatin

KW - Epigenetics

KW - Epithelial-to-mesenchymal transition

KW - Metastasis

UR - http://www.scopus.com/inward/record.url?scp=84899572415&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84899572415&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.1875

DO - 10.18632/oncotarget.1875

M3 - Article

C2 - 24840099

AN - SCOPUS:84899572415

VL - 5

SP - 2016

EP - 2029

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 8

ER -