title: CD147 modulates androgen receptor activity through the Akt/Gsk-3β/β-catenin/AR pathway in prostate cancer cells.
abstract: The androgen signaling pathway serves an important role in the development of prostate cancer. β-Catenin is an androgen receptor (AR) cofactor and augments AR signaling. Glycogen synthase kinase-3β (GSK-3β), a target of phosphorylated serine/threonine protein kinase B (p-Akt), regulates β-catenin stability. In addition, β-catenin, a coregulator of AR, physically interacts with AR and enhances AR-mediated target gene transcription. The multifunctional glycoprotein cluster of differentiation (CD) 147 is highly expressed on the cell surface of the majority of cancer cells, and it promotes tumor invasion, metastasis and growth. In the present study, the molecular effects of CD147 on the Akt/GSK-3β/β-catenin/AR signaling network were investigated in LNCaP cells. Using short hairpin-mediated RNA knockdown of CD147 in LNCaP cells, it was demonstrated that downregulation of CD147 resulted in inhibitory phosphorylation of GSK-3β, and then promoted degeneration of β-catenin and reduced nuclear accumulation of β-catenin. In addition, immunoprecipitation studies demonstrated that CD147 downregulation decreased the formation of a complex between β-catenin and AR. It was shown that CD147 knockdown suppressed the expression of the AR target gene prostate-specific antigen and the growth of AR-positive LNCaP cells. Furthermore, inhibition of PI3K/Akt with LY294002 augmented CD147-mediated function. The present study indicates that the PI3K/Akt pathway may facilitate CD147-mediated activation of the AR pathway.
authors.affiliation: Department of Immunology, Jilin Medical University, Jilin 132013, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Department of Anesthesiology, Affiliated Hospital of Jilin Medical University, Jilin 132011, P.R. China.
authors.forename: Yingxin
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Immunology, Jilin Medical University, Jilin 132013, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Hao
authors.affiliation: Department of Immunology, Jilin Medical University, Jilin 132013, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Jilin Medical University, Jilin 132013, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Jilin Medical University, Jilin 132013, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Immunology, Jilin Medical University, Jilin 132013, P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Immunology, Jilin Medical University, Jilin 132013, P.R. China.
authors.forename: Liangzhong
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Urology Surgery, Affiliated Hospital of Jilin Medical University, Jilin 132011, P.R. China.
authors.forename: Liguo
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Immunology, Jilin Medical University, Jilin 132013, P.R. China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Cai
keywords: Akt; CD147; GSK-3β; androgen receptor; proliferation; prostate cancer; prostate-specific antigen; β-catenin