ERBB receptor activation is required for profibrotic responses to transforming growth factor beta

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Updated: Jun 8, 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

Mahefatiana Andrianifahanana1, Mark C Wilkes, Claire E Repellin

  • 1Thoracic Disease Research Unit, Department of Biochemistry and Molecular Biology, Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.

Cancer Research
|September 16, 2010
PubMed

Insights

Transforming growth factor-β (TGF-β) signaling requires ERBB receptor activation for fibroblast responses. This study reveals ERBB ligands and receptors as critical mediators in TGF-β-induced fibroblast changes.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Transforming growth factor-β (TGF-β) receptor complex engagement initiates critical signaling pathways in health and disease.
  • TGF-β is a key regulator of fibrogenesis and cancer-associated desmoplasia, but its precise mechanisms remain unclear.

Purpose of the Study:

  • To elucidate a novel mechanism of TGF-β action in fibroblasts.
  • To investigate the role of ERBB (epidermal growth factor) receptor family signaling in TGF-β responses.

Main Methods:

  • Investigated TGF-β-induced upregulation of ERBB ligands and receptor activation in fibroblasts.
  • Utilized genetic and pharmacologic approaches to assess ERBB activation.
  • Examined cell type specificity of ERBB activation.

Main Results:

  • TGF-β triggers ERBB ligand upregulation and receptor activation via the SMAD pathway in fibroblasts.
  • ERBB activation is cell type-specific, observed in fibroblasts but not epithelial cells.
  • ERBB activation by TGF-β is essential for fibroblast morphologic transformation and anchorage-independent growth.

Conclusions:

  • Uncovered a novel mechanism where ERBB signaling is required for fibroblast responses to TGF-β.
  • Highlights ERBB ligands/receptors as critical mediators in TGF-β-induced fibroblast pathobiology.

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