WLS-Wnt signaling promotes neuroendocrine prostate cancer
Tyler Bland, Jing Wang, Lijuan Yin, Tianjie Pu, Jingjing Li, Jin Gao, Tzu-Ping Lin, Allen C. Gao, Boyang Jason Wu
Abstract
. 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.
Topics & Concepts
Wnt signaling pathwayProstate cancerCancer researchProstateMediatorAndrogen receptorBiologySecretionCancerIn vivoSignal transductionMedicineCell biologyEndocrinologyGeneticsProstate Cancer Treatment and ResearchCancer-related gene regulationWnt/β-catenin signaling in development and cancer