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Updated: Apr 16, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Ets Related Gene and Smad3 Proteins Collaborate to Activate Transforming Growth Factor-Beta Mediated Signaling

Jinbo Fang1, Huali Xu1, Chunshu Yang1

  • 1Cancer Biology Program, Department of OB/GYN, Morehouse School of Medicine, Georgia Cancer Center for Excellence, Grady Memorial Hospital, 80 Jesse Hill Jr. Drive, Atlanta, GA 30303, USA.

Journal of Pharmaceutical Sciences and Pharmacology
|March 7, 2015
PubMed

Insights

ERG oncoprotein interacts with Smad3, stabilizing it to enhance transforming growth factor-beta (TGF-β)/Smad3 signaling. This interaction promotes prostate cancer development by activating the TGF-β/Smad3 pathway.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • Transforming growth factor-beta (TGF-β)/Smads signaling is crucial for normal and prostate cancer cell growth, regulating proliferation, differentiation, and apoptosis.
  • Receptor-regulated Smads (Smad2/3) complex with Smad4 after phosphorylation, translocating to the nucleus to control gene expression.
  • ERG oncoprotein overexpression, often due to TMPRSS2 gene rearrangement, is linked to aggressive prostate cancer.

Purpose of the Study:

  • To investigate the mechanism by which the ERG oncoprotein influences the TGF-β/Smads signaling pathway, specifically focusing on TGF-β/Smad3 signaling.
  • To elucidate the interaction between ERG and Smad3 in prostate cancer cells.

Main Methods:

  • Studied the effect of ERG on the TGF-β/Smad3 signaling pathway in prostate cells.
  • Investigated the physical interaction between ERG and Smad3 proteins.
  • Assessed the impact of ERG on phospho-Smad3 protein stability.

Main Results:

  • ERG oncoprotein physically interacts with Smad3 protein.
  • ERG stabilizes phospho-Smad3 protein, leading to enhanced TGF-β/Smad3 signaling.
  • ERG activation of TGF-β/Smad3 signaling contributes to prostate tumorigenesis.

Conclusions:

  • ERG oncoprotein activates the TGF-β/Smad3 signaling pathway through a novel mechanism involving Smad3 stabilization.
  • This ERG-mediated activation plays a significant role in prostate cancer development.
Keywords:
ERGPhosphorylationProstate CancerSmad ProteinTGF-β

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