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Updated: Aug 7, 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

Beta3 integrin and Src facilitate transforming growth factor-beta mediated induction of epithelial-mesenchymal

Amy J Galliher1, William P Schiemann

  • 1UCHSC, Fitzsimons Campus, Department of Pharmacology, Mail Stop 8303, RC1 South Tower, Rm L18-6110, PO Box 6511, Aurora, CO 80045, USA. Amy.Galliher@UCHSC.edu

Breast Cancer Research : BCR
|July 25, 2006
PubMed
Abstract

Insights

Beta3 integrin promotes breast cancer metastasis by altering transforming growth factor (TGF)-beta signaling. Targeting beta3 integrin may restore TGF-beta

Area of Science:

  • Cell biology
  • Molecular oncology
  • Cancer research

Background:

  • Transforming growth factor (TGF)-beta normally suppresses breast cancer by halting cell cycle progression in mammary epithelial cells (MECs).
  • During tumor development, genetic and epigenetic changes in MECs can reverse TGF-beta's tumor-suppressive role, promoting metastasis.
  • The mechanisms behind this functional switch in TGF-beta signaling are not fully understood but may involve integrin signaling.

Purpose of the Study:

  • To investigate the role of beta3 integrin in modulating TGF-beta signaling in MECs.
  • To determine how beta3 integrin influences TGF-beta-induced epithelial-mesenchymal transition (EMT), invasion, and cell proliferation.
  • To elucidate the involvement of Src kinase in beta3 integrin-mediated alterations of TGF-beta signaling.

Main Methods:

  • Manipulated beta3 integrin expression or function in MECs using retroviral transduction and small interfering RNA (siRNA).
  • Assessed TGF-beta-stimulated proliferation, invasion, and EMT in MECs with altered beta3 integrin levels.
  • Investigated Src kinase involvement through protein kinase assays and pharmacological/genetic inhibition.

Main Results:

  • TGF-beta stimulation induced beta3 integrin expression, coinciding with EMT.
  • siRNA-mediated knockdown of beta3 integrin blocked TGF-beta-induced EMT.
  • Beta3 integrin physically interacted with TGF-beta receptor type II (TbetaR-II), enhancing MAPK and Smad2/3 signaling.
  • This interaction blocked TGF-beta-induced growth arrest and promoted invasion and EMT.
  • Src kinase mediated TbetaR-II tyrosine phosphorylation upon beta3 integrin:TbetaR-II complex formation, driving MAPK activation and EMT.
  • Inhibition of Src blocked beta3 integrin's ability to promote TGF-beta-induced EMT and invasion.
  • Beta3 integrin expression enhanced TGF-beta-stimulated invasion in human breast cancer cells, while a mutant form abolished this effect.

Conclusions:

  • Beta3 integrin promotes breast cancer progression by altering TGF-beta signaling through Src-mediated TbetaR-II tyrosine phosphorylation.
  • This interaction enhances TGF-beta's ability to induce EMT and invasion.
  • Targeting beta3 integrin may offer a novel therapeutic strategy to restore TGF-beta's tumor-suppressive functions in advanced breast cancers.

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