Single-cell analysis identifies LY6D as a marker linking castration-resistant prostate luminal cells to prostate progenitors and cancer
AuthorsBarros-Silva, Joao D
Brown, Michael D
Clarke, Noel W
AffiliationProstate Oncobiology, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park SK10 4TG, UK
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AbstractThe exact identity of castrate-resistant (CR) cells and their relation to CR prostate cancer (CRPC) is unresolved. We use single-cell gene profiling to analyze the molecular heterogeneity in basal and luminal compartments. Within the luminal compartment, we identify a subset of cells intrinsically resistant to castration with a bi-lineage gene expression pattern. We discover LY6D as a marker of CR prostate progenitors with multipotent differentiation and enriched organoid-forming capacity. Lineage tracing further reveals that LY6D+ CR luminal cells can produce LY6D- luminal cells. In contrast, in luminal cells lacking PTEN, LY6D+ cells predominantly give rise to LY6D+ tumor cells, contributing to high-grade PIN lesions. Gene expression analyses in patients' biopsies indicate that LY6D expression correlates with early disease progression, including progression to CRPC. Our studies thus identify a subpopulation of luminal progenitors characterized by LY6D expression and intrinsic castration resistance. LY6D may serve as a prognostic maker for advanced prostate cancer.
CitationBarros-Silva JD, Linn DE, Steiner I, Guo G, Ali A, Pakula H, et al. Single-cell analysis identifies LY6D as a marker linking castration-resistant prostate luminal cells to prostate progenitors and cancer. Cell Rep. 2018 Dec 18;25(12):3504-18 e6.