Wnt signaling promotes androgen-independent prostate cancer cell proliferation through up-regulation of the hippo pathway effector YAP.
Biochem Biophys Res Commun
; 486(4): 1034-1039, 2017 05 13.
Article
em En
| MEDLINE
| ID: mdl-28366633
ABSTRACT
Aberrant up-regulation of Wnt/ß-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/ß-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 ß-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/ß-catenin and Hippo pathways in androgen-independent prostate cancer development.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
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Neoplasias da Próstata
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Proteínas Serina-Treonina Quinases
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Proteínas Adaptadoras de Transdução de Sinal
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Proliferação de Células
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Proteína Wnt3A
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Androgênios
Limite:
Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article