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

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P21 activated kinase-1 mediates transforming growth factor β1-induced prostate cancer cell epithelial to mesenchymal

Ahmad Al-Azayzih1, Fei Gao2, Payaningal R Somanath3

  • 1Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia and Charlie Norwood VA Medical Center, Augusta, GA, United States; College of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.

Biochimica Et Biophysica Acta
|March 10, 2015
PubMed

Insights

Transforming growth factor beta (TGFβ) plays a dual role in prostate cancer. Targeting the TGFβ-Pak1 pathway may offer therapeutic benefits for advanced prostate cancer by inhibiting EMT.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Transforming growth factor beta (TGFβ) has a complex role in prostate cancer, suppressing early growth but promoting epithelial-to-mesenchymal transition (EMT) in advanced stages.
  • The precise molecular mechanisms underlying TGFβ1's dual role, particularly its induction of EMT, remain unclear.

Purpose of the Study:

  • To investigate the role of P21-activated kinase 1 (Pak1) in mediating TGFβ1-induced EMT in prostate cancer.
  • To explore the potential of targeting the TGFβ1-Pak1 pathway as a therapeutic strategy for advanced prostate cancer.

Main Methods:

  • Utilized prostate cancer cell lines (PC3, DU145) and in vivo xenograft models.
  • Investigated the effects of TGFβ1 stimulation with and without Pak1 inhibition (using IPA 3 or siRNA).
  • Assessed tumor growth, apoptosis, cell scattering, and expression of EMT markers (Snail, N-cadherin).

Main Results:

  • TGFβ1 inhibited PC3 tumor xenograft growth through P38-MAPK and caspase activation.
  • Long-term TGFβ1 stimulation induced EMT markers via TRAF6-mediated Rac1/Pak1 activation.
  • Pak1 inhibition (IPA 3 or siRNA) significantly blocked TGFβ1-induced EMT and mesenchymal marker expression.

Conclusions:

  • TGFβ1 induces apoptosis via P38-MAPK and EMT via Rac1/Pak1 in prostate cancer cells.
  • Pak1 is essential for TGFβ1-induced EMT in prostate cancer.
  • Targeting the TGFβ1-Pak1 pathway presents a potential therapeutic avenue for advanced prostate cancer.
Keywords:
EMTPak1Prostate cancerSnailTGFβ

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