WLS-Wnt signaling promotes neuroendocrine prostate cancer

WLS-Wnt signaling promotes neuroendocrine prostate cancer

Summary: Neuroendocrine prostate cancer (NEPC) is a lethal prostate cancer subtype arising as a consequence of more potent androgen receptor (AR) targeting in castration-resistant prostate cancer (CRPC). Its molecular pathogenesis remains elusive. Here, we report that the Wnt secretion mediator Wntl...

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Bibliographic Details
Main Authors: Tyler Bland, Jing Wang, Lijuan Yin, Tianjie Pu, Jingjing Li, Jin Gao, Tzu-Ping Lin, Allen C. Gao, Boyang Jason Wu
Format: Article
Language:English
Published: Elsevier 2021-01-01
Series:iScience
Subjects:
Biological Sciences
Cell Biology
Cancer
Transcriptomics
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004220311676
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Summary:Summary: Neuroendocrine prostate cancer (NEPC) is a lethal prostate cancer subtype arising as a consequence of more potent androgen receptor (AR) targeting in castration-resistant prostate cancer (CRPC). Its molecular pathogenesis remains elusive. Here, we report that the Wnt secretion mediator Wntless (WLS) is a major driver of NEPC and aggressive tumor growth in vitro and in vivo. Mechanistic studies showed that WLS is a transcriptional target suppressed by AR that activates the ROR2/PKCδ/ERK signaling pathway to support the neuroendocrine (NE) traits and proliferative capacity of NEPC cells. Analysis of clinical samples and datasets revealed that WLS was highly expressed in CRPC and NEPC tumors. Finally, treatment with the Wnt secretion inhibitor LGK974 restricted NE prostate tumor xenograft growth in mice. These findings collectively characterize the contribution of WLS to NEPC pathogenesis and suggest that WLS is a potential therapeutic target in NEPC.
ISSN:2589-0042

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