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Wnt signaling promotes androgen-independent prostate cancer cell proliferation through up-regulation of the hippo pathway effector YAP.
Biochem Biophys Res Commun. 2017 05 13; 486(4):1034-1039.BB

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+Show Affiliations

Department of Urology, Busan Paik Hospital, Inje University 633-165, Busan 47392, Republic of Korea.Department of Bio and Fermentation Convergence Technology, Kookmin University, BK21 PLUS Program, Seoul 02707, Republic of Korea.Department of Life Science, Sogang University, Seoul 04107, Republic of Korea.Department of Life Science, Sogang University, Seoul 04107, Republic of Korea.Department of Urology, Busan Paik Hospital, Inje University 633-165, Busan 47392, Republic of Korea.Department of Urology, Kosin University Gospel Hospital, Busan, Republic of Korea.Department of Bio and Fermentation Convergence Technology, Kookmin University, BK21 PLUS Program, Seoul 02707, Republic of Korea. Electronic address: ohsa@kookmin.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28366633

Citation

Seo, Won Ik, et al. "Wnt Signaling Promotes Androgen-independent Prostate Cancer Cell Proliferation Through Up-regulation of the Hippo Pathway Effector YAP." Biochemical and Biophysical Research Communications, vol. 486, no. 4, 2017, pp. 1034-1039.
Seo WI, Park S, Gwak J, et al. Wnt signaling promotes androgen-independent prostate cancer cell proliferation through up-regulation of the hippo pathway effector YAP. Biochem Biophys Res Commun. 2017;486(4):1034-1039.
Seo, W. I., Park, S., Gwak, J., Ju, B. G., Chung, J. I., Kang, P. M., & Oh, S. (2017). Wnt signaling promotes androgen-independent prostate cancer cell proliferation through up-regulation of the hippo pathway effector YAP. Biochemical and Biophysical Research Communications, 486(4), 1034-1039. https://doi.org/10.1016/j.bbrc.2017.03.158
Seo WI, et al. Wnt Signaling Promotes Androgen-independent Prostate Cancer Cell Proliferation Through Up-regulation of the Hippo Pathway Effector YAP. Biochem Biophys Res Commun. 2017 05 13;486(4):1034-1039. PubMed PMID: 28366633.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Wnt signaling promotes androgen-independent prostate cancer cell proliferation through up-regulation of the hippo pathway effector YAP. AU - Seo,Won Ik, AU - Park,Seoyoung, AU - Gwak,Jungsug, AU - Ju,Bong Gun, AU - Chung,Jae Il, AU - Kang,Pil Moon, AU - Oh,Sangtaek, Y1 - 2017/03/30/ PY - 2017/03/23/received PY - 2017/03/29/accepted PY - 2017/4/4/pubmed PY - 2017/6/13/medline PY - 2017/4/4/entrez KW - Androgen receptor (AR) KW - Hippo signaling KW - Prostate cancer KW - Wnt/β-catenin signaling KW - Yes-associated protein (YAP) SP - 1034 EP - 1039 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 486 IS - 4 N2 - 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. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/28366633/Wnt_signaling_promotes_androgen_independent_prostate_cancer_cell_proliferation_through_up_regulation_of_the_hippo_pathway_effector_YAP_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(17)30635-6 DB - PRIME DP - Unbound Medicine ER -