Wntless expression promotes lineage plasticity and is associated with neuroendocrine prostate cancer.

Autor:	D'Abronzo LS; Department of Urologic Surgery, University of California Davis Sacramento, California, USA., Lombard AP; Department of Urologic Surgery, University of California Davis Sacramento, California, USA.; UC Davis Comprehensive Cancer Center, University of California Davis Sacramento, California, USA.; Department of Biochemistry and Molecular Medicine, University of California Davis Sacramento, California, USA., Ning S; Department of Urologic Surgery, University of California Davis Sacramento, California, USA., Armstong CM; Department of Urologic Surgery, University of California Davis Sacramento, California, USA., Leslie AR; Department of Urologic Surgery, University of California Davis Sacramento, California, USA., Sharifi M; Department of Urologic Surgery, University of California Davis Sacramento, California, USA., Schaaf ZA; Department of Urologic Surgery, University of California Davis Sacramento, California, USA., Lou W; Department of Urologic Surgery, University of California Davis Sacramento, California, USA., Gao AC; Department of Urologic Surgery, University of California Davis Sacramento, California, USA.; UC Davis Comprehensive Cancer Center, University of California Davis Sacramento, California, USA.; VA Northern California Health Care System Sacramento, California, USA.
Jazyk:	angličtina
Zdroj:	American journal of clinical and experimental urology [Am J Clin Exp Urol] 2022 Oct 15; Vol. 10 (5), pp. 299-310. Date of Electronic Publication: 2022 Oct 15 (Print Publication: 2022).
Abstrakt:	Resistance to androgen receptor (AR) targeted therapies remains as the main reason for most prostate cancer related deaths. Lineage plasticity resulting in altered, treatment insensitive prostate tumor cell phenotypes such neuroendocrine differentiated prostate cancer is a common manifestation within resistant tumors upon AR-targeted therapies. The mechanisms responsible for lineage plasticity in prostate cancer remain incompletely understood. Here we demonstrate that the enzalutamide resistant MDVR cell line possesses lineage plastic characteristics associated with overexpression of the Wnt transporter Wntless (WLS). Furthermore, we present evidence that overexpression of WLS is common in varying cell line models of lineage plastic prostate cancer, is higher in neuroendocrine patient samples, and positively correlates with the neuroendocrine marker SYP in clinical data. Targeting WLS in lineage plastic cellular models reduces viability and represses lineage plasticity associated gene expression. Our study provides insight into the importance of WLS to the development of lethal resistant prostate cancer and provides a potential target for the treatment of advanced disease. Competing Interests: None. (AJCEU Copyright © 2022.)
Databáze:	MEDLINE
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