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Updated: Apr 19, 2026

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

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Blocking TGF-β inhibits breast cancer cell invasiveness via ERK/S100A4 signal

X G Wang1, Q Meng, F M Qi

  • 1Breast Surgery, Qilu Hospital, Shandong University, Jinan, China. yangqifeng7@163.com.

European Review for Medical and Pharmacological Sciences
|January 4, 2015
PubMed
Abstract

Insights

Targeting transforming growth factor-beta (TGF-β) inhibits breast cancer cell invasion and metastasis. This study reveals TGF-β regulates S100A4 through ERK1/2 signaling, impacting tumor cell invasiveness.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Transforming growth factor-beta (TGF-β) plays a critical role in breast cancer progression, particularly in invasion and metastasis.
  • The precise molecular mechanisms by which TGF-β mediates these effects are not fully understood.
  • Identifying key signaling pathways is crucial for developing targeted therapies.

Purpose of the Study:

  • To elucidate the mechanism of TGF-β-mediated tumor invasion in breast cancer cells.
  • To investigate the role of ERK1/2 and S100A4 in TGF-β-induced invasion.
  • To explore the potential of targeting the TGF-β pathway for breast cancer treatment.

Main Methods:

  • Stable transfection of MDA-MB-231 breast cancer cells with TGF-β1 small interfering RNA (siRNA).
  • In vitro assays including wound-healing (migration), Boyden chamber transwell (invasion), and angiogenesis assays.
  • Pharmacological inhibition of ERK1/2 using PD98059 and S100A4 knockdown via siRNA.
  • Analysis of TGF-β signaling pathway activation, specifically p-ERK1/2 levels and S100A4 expression.

Main Results:

  • Down-regulation of TGF-β1 significantly reduced migration, invasion, and angiogenesis in MDA-MB-231 cells.
  • Restoration of TGF-β1 levels in TGF-β1 siRNA-transfected cells re-established invasive capabilities.
  • Inhibition of ERK1/2 or S100A4 abolished TGF-β1-induced increases in migration, invasion, and angiogenesis.
  • TGF-β1 was found to regulate S100A4 expression through the ERK1/2 signaling pathway.

Conclusions:

  • TGF-β signaling, via the ERK/S100A4 pathway, is a key driver of breast cancer cell invasiveness, migration, and angiogenesis.
  • Blocking TGF-β signaling effectively inhibits these processes in vitro.
  • Targeting the TGF-β pathway presents a promising therapeutic strategy to prevent breast cancer progression.

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