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Updated: Jun 19, 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

p130Cas is required for mammary tumor growth and transforming growth factor-beta-mediated metastasis through

Michael K Wendt1, Jason A Smith, William P Schiemann

  • 1Department of Pharmacology, University of Colorado, Denver, Anschutz Medical Campus, Aurora, Colorado 80045, USA.

The Journal of Biological Chemistry
|October 14, 2009
PubMed

Insights

p130Cas regulates transforming growth factor-beta (TGF-beta) signaling in breast cancer. Aberrant p130Cas expression shifts TGF-beta from tumor suppression to promoting metastasis by altering its signaling pathways.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Transforming growth factor-beta (TGF-beta) function shifts during breast cancer progression, transitioning from tumor suppression to promoting metastasis.
  • This functional conversion is linked to alterations in TGF-beta signaling pathways.

Purpose of the Study:

  • To investigate the role of the focal adhesion protein p130Cas in mediating TGF-beta signaling changes during breast cancer progression.
  • To determine how p130Cas influences the balance between canonical (Smad2/3) and noncanonical (p38 MAPK) TGF-beta signaling pathways.

Main Methods:

  • Manipulating p130Cas expression (full-length and carboxyl terminus) in mammary epithelial cells (MECs).
  • Assessing TGF-beta1-induced activation of Smad2/3 and p38 MAPK.
  • Utilizing three-dimensional organotypic cultures and in vivo mouse models to evaluate cellular behavior and tumor growth.
  • Examining the impact of TbetaR-II expression and p130Cas depletion on TGF-beta signaling and metastasis.

Main Results:

  • Elevated p130Cas (FL or CT) in MECs reduced Smad2/3 activation but increased p38 MAPK coupling, leading to resistance to TGF-beta-induced growth arrest and altered acinar morphology.
  • p130Cas deficiency in metastatic MECs enhanced Smad2/3 activity, restoring TGF-beta-mediated growth inhibition in vitro and in vivo.
  • In metastatic MECs, TbetaR-II expression enhanced p38 MAPK activation, promoting invasion and metastasis, while p130Cas depletion restored Smad2/3 activity and reversed TGF-beta-stimulated invasion.

Conclusions:

  • p130Cas acts as a molecular rheostat, controlling the balance between canonical and noncanonical TGF-beta signaling.
  • This balance is crucial for maintaining TGF-beta's tumor suppressor function during breast cancer progression.
  • Targeting p130Cas may offer a strategy to restore TGF-beta's anti-tumor activity and combat metastasis.

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