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Updated: Jun 16, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

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

Published on: October 27, 2020

Smad signaling is required to maintain epigenetic silencing during breast cancer progression

Panagiotis Papageorgis1, Arthur W Lambert, Sait Ozturk

  • 1Departments of Medicine (Genetics and Molecular Medicine Programs and Cancer Research Center), Genetics and Genomics, Boston University School of Medicine, Boston, Massachusetts, USA.

Cancer Research
|January 21, 2010
PubMed

Insights

Transforming growth factor beta (TGFbeta) signaling maintains breast cancer progression by epigenetically silencing epithelial genes. Disrupting this pathway reverses silencing, restoring epithelial traits and reducing invasion.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Epigenetics

Background:

  • Breast cancer progression involves epithelial-mesenchymal transition (EMT), linked to altered DNA methylation and gene expression.
  • The mechanisms driving aberrant DNA methylation machinery activation during EMT remain unclear.

Purpose of the Study:

  • To investigate the role of transforming growth factor beta (TGFbeta) signaling in maintaining epigenetic silencing of EMT-related genes in breast cancer.
  • To explore the potential of targeting the TGFbeta pathway for reversing epigenetic changes and suppressing cancer progression.

Main Methods:

  • Utilized a breast cancer cell model undergoing EMT.
  • Analyzed gene expression, DNA methylation, and TGFbeta-Smad signaling.
  • Investigated the effect of disrupting Smad signaling on DNA methylation and gene reexpression.
  • Assessed changes in cell morphology and invasive properties.
  • Measured DNA methyltransferase (DNMT1) activity.

Main Results:

  • EMT-associated breast cancer cells showed overactive TGFbeta signaling and hypermethylation, silencing CDH1, CGN, CLDN4, and KLK10 genes.
  • Disrupting Smad signaling led to DNA demethylation and reexpression of these silenced genes.
  • Reversal of epigenetic silencing was accompanied by a shift to epithelial morphology and reduced invasion.
  • TGFbeta pathway inhibition decreased DNMT1 activity, indicating impaired maintenance of DNA methylation.

Conclusions:

  • A hyperactive TGFbeta-TGFbetaR-Smad2 signaling axis is crucial for maintaining epigenetic silencing of EMT genes in breast cancer.
  • Targeting this axis can reverse epigenetic silencing, suppress invasion, and potentially halt breast cancer progression.

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