OVOL2 antagonizes TGF-β signaling to regulate epithelial to mesenchymal transition during mammary tumor metastasis

Rong-Si Wu1,2, Jing-Jing Hong1,2, Jia-Fa Wu1,3

  • 1State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.

Oncotarget
|April 30, 2017
PubMed

Insights

OVOL2, a transcription factor, inhibits epithelial-mesenchymal transition (EMT) in breast cancer by suppressing TGF-β signaling. Restoring OVOL2 may offer a strategy to reduce mammary tumor invasion and metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Transforming growth factor-beta (TGF-β) signaling drives epithelial-mesenchymal transition (EMT), crucial for cancer metastasis.
  • The precise regulation of TGF-β signaling during mammary tumor metastasis remains incompletely understood.

Purpose of the Study:

  • To investigate the role of OVOL2 in regulating TGF-β signaling-induced EMT in breast cancer.
  • To elucidate the molecular mechanisms by which OVOL2 influences TGF-β signaling pathways.

Main Methods:

  • Utilized mouse and human mammary tumor cells and mouse tumor models.
  • Analyzed OVOL2 expression in relation to breast cancer progression using Oncomine databases.
  • Performed molecular experiments to assess OVOL2's impact on TGF-β signaling components (Smad4, Smad7, Smad2/3).

Main Results:

  • OVOL2 significantly inhibits TGF-β signaling-induced EMT in mammary tumor cells and models.
  • OVOL2 expression negatively correlates with breast cancer progression.
  • OVOL2 interferes with TGF-β signaling by modulating Smad4 and Smad7 mRNA levels and disrupting Smad complex formation and DNA binding.

Conclusions:

  • OVOL2 acts as a novel inhibitor of TGF-β signaling, controlling its output at multiple molecular levels.
  • Restoring OVOL2 expression presents a potential therapeutic strategy to inhibit breast cancer invasion and metastasis.

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