title: Wnt signaling promotes androgen-independent prostate cancer cell proliferation through up-regulation of the hippo pathway effector YAP.
abstract: Aberrant up-regulation of Wnt/β-catenin signaling is associated with the development and progression of prostate cancer, but the underlying mechanism is unclear. Here we show that in the absence of androgens, the Wnt/β-catenin pathway activates AR-mediated transcription through up-regulation of the Hippo pathway effector Yes-associated protein (YAP). Wnt3a-conditioned medium (Wnt3a-CM) promotes the growth of LNCaP cells and increases AR and YAP protein levels. Moreover, Wnt3a-CM induces the nuclear translocation of YAP and the AR, but not β-catenin, thereby activating the expression of AR- and YAP-dependent genes, in an androgen-independent manner. In addition, depletion of YAP with small interfering RNA (siRNA) prevented Wnt3a-CM-mediated up-regulation of AR-dependent gene expression. Thus, our findings provide mechanistic insight into the proposed cross-talk between the Wnt/β-catenin and Hippo pathways in androgen-independent prostate cancer development.
authors.affiliation: Department of Urology, Busan Paik Hospital, Inje University 633-165, Busan 47392, Republic of Korea.
authors.forename: Won Ik
authors.initials: WI
authors.lastname: Seo
authors.affiliation: Department of Bio and Fermentation Convergence Technology, Kookmin University, BK21 PLUS Program, Seoul 02707, Republic of Korea.
authors.forename: Seoyoung
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Life Science, Sogang University, Seoul 04107, Republic of Korea.
authors.forename: Jungsug
authors.initials: J
authors.lastname: Gwak
authors.affiliation: Department of Life Science, Sogang University, Seoul 04107, Republic of Korea.
authors.forename: Bong Gun
authors.initials: BG
authors.lastname: Ju
authors.affiliation: Department of Urology, Busan Paik Hospital, Inje University 633-165, Busan 47392, Republic of Korea.
authors.forename: Jae Il
authors.initials: JI
authors.lastname: Chung
authors.affiliation: Department of Urology, Kosin University Gospel Hospital, Busan, Republic of Korea.
authors.forename: Pil Moon
authors.initials: PM
authors.lastname: Kang
authors.affiliation: Department of Bio and Fermentation Convergence Technology, Kookmin University, BK21 PLUS Program, Seoul 02707, Republic of Korea. Electronic address: ohsa@kookmin.ac.kr.
authors.forename: Sangtaek
authors.initials: S
authors.lastname: Oh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000728:Androgens / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000090683:Hippo Signaling Pathway; D006801:Humans; D008297:Male; D010750:Phosphoproteins / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011944:Receptors, Androgen; D014157:Transcription Factors; D015854:Up-Regulation; D060449:Wnt Signaling Pathway; D060509:Wnt3A Protein / Q000378:metabolism*; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000728:Androgens; D010750:Phosphoproteins; D011944:Receptors, Androgen; D014157:Transcription Factors; C555510:WNT3A protein, human; D060509:Wnt3A Protein; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Androgen receptor (AR); Hippo signaling; Prostate cancer; Wnt/β-catenin signaling; Yes-associated protein (YAP)