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Updated: Feb 23, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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FGFR2-Driven Signaling Counteracts Tamoxifen Effect on ERα-Positive Breast Cancer Cells

Lukasz Turczyk1, Kamila Kitowska1, Magdalena Mieszkowska1

  • 1Department of Molecular Enzymology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdansk, Poland.

Neoplasia (New York, N.Y.)
|September 5, 2017
PubMed

Insights

Fibroblast Growth Factors (FGFs), particularly FGF7, promote breast cancer growth and tamoxifen resistance by activating FGFR2. This signaling pathway degrades estrogen receptors, counteracting endocrine therapy effectiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Endocrine therapy resistance is a major challenge in breast cancer treatment.
  • Growth factor receptor signaling is implicated in treatment failure.

Purpose of the Study:

  • To investigate the role of Fibroblast Growth Factors (FGFs) and their receptors in tamoxifen resistance in breast cancer.
  • To elucidate the molecular mechanisms by which FGF signaling contributes to endocrine therapy failure.

Main Methods:

  • In vitro studies using breast cancer cell lines treated with tamoxifen and FGFs.
  • Identification of FGF7 as a key mediator and FGFR2 as its receptor.
  • Analysis of downstream signaling pathways including ER phosphorylation, ubiquitination, and degradation.
  • Investigation of PI3K/AKT signaling and Bcl-2 expression.
  • Correlation analysis of FGFR2 and ER expression in patient tissue samples.

Main Results:

  • FGF7 significantly promotes breast cancer cell growth in the presence of tamoxifen.
  • FGFR2 mediates FGF7 action, leading to tamoxifen resistance.
  • FGF7/FGFR2 signaling induces estrogen receptor (ER) phosphorylation, ubiquitination, and proteasomal degradation.
  • This ER degradation counteracts tamoxifen-induced ER stabilization.
  • Activation of PI3K/AKT signaling and altered Bcl-2 expression are involved in FGFR2-mediated resistance.
  • An inverse correlation between FGFR2 and ER expression was observed in patient tissues.

Conclusions:

  • FGFR2-mediated signaling plays a critical role in promoting breast cancer cell growth and resistance to tamoxifen.
  • The FGF7/FGFR2 pathway contributes to endocrine therapy failure by destabilizing the estrogen receptor.
  • These findings highlight the complex interplay between growth factor signaling and ER regulation in breast cancer.

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