Single-Cell Analysis Identifies LY6D as a Marker Linking Castration-Resistant Prostate Luminal Cells to Prostate Progenitors and Cancer. Academic Article uri icon

Overview

abstract

  • The 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.

publication date

  • December 18, 2018

Research

keywords

  • Biomarkers, Tumor
  • Cell Adhesion Molecules
  • Neoplastic Stem Cells
  • Prostate
  • Prostatic Neoplasms, Castration-Resistant
  • Single-Cell Analysis

Identity

PubMed Central ID

  • PMC6315111

Scopus Document Identifier

  • 85058168580

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2018.11.069

PubMed ID

  • 30566873

Additional Document Info

volume

  • 25

issue

  • 12