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CD147 modulates androgen receptor activity through the Akt/Gsk-3β/β-catenin/AR pathway in prostate cancer cells

Fang Fang1, Yingxin Qin2, Feng Hao1

  • 1Department of Immunology, Jilin Medical University, Jilin 132013, P.R. China.

Oncology Letters
|July 23, 2016
PubMed

Insights

Cluster of differentiation (CD) 147 promotes prostate cancer by activating the androgen receptor (AR) pathway. Inhibiting CD147 reduces AR signaling, prostate-specific antigen expression, and LNCaP cell growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • The androgen signaling pathway is crucial in prostate cancer development.
  • Beta-catenin (β-catenin) acts as an androgen receptor (AR) cofactor, enhancing AR signaling.
  • Cluster of differentiation (CD) 147 is a glycoprotein overexpressed in cancers, promoting tumor progression.

Purpose of the Study:

  • To investigate the molecular effects of CD147 on the Akt/GSK-3β/β-catenin/AR signaling network in LNCaP cells.
  • To elucidate the role of CD147 in regulating AR signaling and prostate cancer cell growth.

Main Methods:

  • Short hairpin RNA (shRNA) mediated knockdown of CD147 in LNCaP cells.
  • Western blotting and immunoprecipitation to analyze protein interactions and phosphorylation.
  • Quantitative analysis of AR target gene expression (prostate-specific antigen) and cell proliferation.

Main Results:

  • CD147 knockdown led to inhibitory phosphorylation of GSK-3β, promoting β-catenin degradation and reducing nuclear accumulation.
  • Downregulation of CD147 decreased the physical interaction between β-catenin and AR.
  • CD147 knockdown suppressed prostate-specific antigen expression and LNCaP cell growth.
  • Inhibition of PI3K/Akt pathway augmented CD147-mediated effects.

Conclusions:

  • CD147 plays a significant role in activating the androgen receptor pathway in prostate cancer cells.
  • The PI3K/Akt pathway mediates CD147's function in activating the AR pathway.
  • Targeting CD147 may represent a therapeutic strategy for prostate cancer.
Keywords:
AktCD147GSK-3βandrogen receptorproliferationprostate cancerprostate-specific antigenβ-catenin

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