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Updated: Jun 17, 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

Published on: October 27, 2020

Smad2 and Smad3 have opposing roles in breast cancer bone metastasis by differentially affecting tumor angiogenesis

M Petersen1, E Pardali, G van der Horst

  • 1Department of Molecular Cell Biology and Centre for Biomedical Genetics, Leiden, The Netherlands.

Oncogene
|December 17, 2009
PubMed

Insights

Transforming growth factor-beta (TGF-β) has dual roles in breast cancer. This study reveals Smad2 and Smad3 proteins differentially regulate TGF-β

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Transforming growth factor-beta (TGF-β) exhibits dichotomous functions in breast cancer progression, acting as both a suppressor and promoter.
  • The precise roles of intracellular effector proteins Smad2 and Smad3 in mediating TGF-β's opposing effects on breast cancer remain incompletely understood.

Purpose of the Study:

  • To elucidate the specific functions of Smad2 and Smad3 in mediating TGF-β-induced responses within breast cancer cells.
  • To investigate the in vivo roles of Smad2 and Smad3 in a mouse model of breast cancer bone metastasis.

Main Methods:

  • Stable knockdown of Smad2 or Smad3 expression in MDA-MB-231 breast cancer cells.
  • Assessment of TGF-β-induced transcriptional responses, including vascular endothelial growth factor (VEGF) expression.
  • Evaluation of bone metastasis formation and tumor angiogenesis in a mouse model.

Main Results:

  • Smad3 knockdown mitigated TGF-β-induced transcriptional responses, while Smad2 knockdown enhanced them.
  • TGF-β induction of bone metastasis-related genes was Smad3-dependent.
  • Smad3 knockdown delayed bone metastasis, whereas Smad2 knockdown promoted a more aggressive metastatic phenotype and increased tumor angiogenesis.

Conclusions:

  • Smad2 and Smad3 play distinct and opposing roles in regulating TGF-β's effects on breast cancer bone metastasis.
  • Differential regulation of tumor angiogenesis by Smad2 and Smad3 underlies their opposing roles in metastasis.

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