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Updated: Mar 28, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

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Context-Specific Effects of TGF-β/SMAD3 in Cancer Are Modulated by the Epigenome

Ana Tufegdzic Vidakovic1, Oscar M Rueda1, Stephin J Vervoort2

  • 1Cancer Research UK Cambridge Institute, Department of Oncology, University of Cambridge, Cambridge CB2 0RE, UK.

Cell Reports
|December 22, 2015
PubMed

Insights

The epigenome dictates how transforming growth factor beta (TGF-β) signaling affects cancer. Distinct epigenomes in breast-tumor-initiating cells (BTICs) determine if TGF-β promotes or suppresses tumors.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • The transforming growth factor beta (TGF-β) signaling pathway has dual roles in cancer, acting as both a tumor promoter and suppressor.
  • The precise mechanisms underlying these opposing effects remain incompletely understood, particularly in the context of cancer stem cells.

Purpose of the Study:

  • To investigate the role of the epigenome in mediating the context-specific effects of TGF-β signaling in breast-tumor-initiating cells (BTICs).
  • To elucidate the interplay between SMAD3, a key downstream effector, and cellular epigenomes in determining TGF-β pathway outcomes in cancer.

Main Methods:

  • Analysis of genomic SMAD3 binding patterns in different BTIC contexts.
  • Assessment of cell-type-specific DNA and histone modifications.
  • Investigation of gene expression programs associated with TGF-β signaling.
  • Functional studies on context-specific target genes, such as LBH, including DNA methylation analysis.

Main Results:

  • Genomic SMAD3 binding patterns were similar across both tumor-promoting and tumor-suppressing BTIC contexts.
  • Distinct patterns of DNA and histone modifications in BTICs modulate gene accessibility to TGF-β/SMAD3 regulation.
  • The gene LBH, identified as a context-specific target, demonstrated regulation via DNA methylation and was critical for TGF-β-mediated BTIC promotion.

Conclusions:

  • The epigenome plays a critical, previously underappreciated role in determining the opposing functions of TGF-β signaling in cancer.
  • Epigenetic modifications provide a layer of regulation that dictates cellular responses to TGF-β/SMAD3, impacting cancer progression.

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