Wnt signaling promotes androgen-independent prostate cancer cell proliferation through up-regulation of the hippo pathway effector YAP
- Department of Urology, Busan Paik Hospital, Inje University 633-165, Busan 47392 (Korea, Republic of)
- Department of Bio and Fermentation Convergence Technology, Kookmin University, BK21 PLUS Program, Seoul 02707 (Korea, Republic of)
- Department of Life Science, Sogang University, Seoul 04107 (Korea, Republic of)
- Department of Urology, Kosin University Gospel Hospital, Busan (Korea, Republic of)
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. - Highlights: • Wnt3a promotes androgen-independent prostate cancer cell growth. • Wnt3a activates YAP- and AR-mediated transcription in the absence of androgen. • YAP is required for Wnt3a-induced AR activation in the absence of androgen.
- OSTI ID:
- 22697011
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 486, Issue 4; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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