Type 2 fibroblast growth factor receptor signaling preserves stemness and prevents differentiation of prostate stem cells from the basal compartment

Yanqing Huang, Tomoaki Hamana, Junchen Liu, Cong Wang, Lei An, Pan You, Julia Y.F. Chang, Jianming Xu, Chengliu Jin, Zhongying Zhang, Wallace L. McKeehan, Fen Wang

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Prostate stem cells (P-SCs) are capable of giving rise to all three lineages of prostate epithelial cells, which include basal, luminal, and neuroendocrine cells. Two types of P-SCs have been identified in both human and mouse adult prostates based on prostasphere or organoid cultures, cell lineage tracing, renal capsule implantation, and expression of luminal- and basal-specific proteins. The sphere-forming P-SCs are from the basal cell compartment that express P63, and are therefore designated as basal P-SCs (P-bSCs). Luminal P-SCs (P-lSCs) express luminal cytokeratins and Nkx3.1. Herein, we report that the type 2 FGF receptor (FGFR2) signaling axis is crucial for preserving stemness and preventing differentiation of P-bSCs. FGFR2 signaling mediated by FGFR substrate 2α (FRS2α) is indispensable for formation and maintenance of prostaspheres derived from P63+ P-bSCs. Ablation of Fgfr2 in P63+ cells in vitro causes the disintegration of prostaspheres. Ablation of Fgfr2 in vivo reduces the number of P63-expressing basal cells and enriches luminal cells. This suggests a basal stem cell-to-luminal cell differentiation. In addition, ablation of Fgfr2 in P63+ cells causes defective postnatal development of the prostate. Therefore, the data indicate that FGFR2 signaling is critical for preserving stemness and preventing differentiation of P-bSCs.

Original languageEnglish (US)
Pages (from-to)17753-17761
Number of pages9
JournalJournal of Biological Chemistry
Volume290
Issue number29
DOIs
StatePublished - Jul 17 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Type 2 fibroblast growth factor receptor signaling preserves stemness and prevents differentiation of prostate stem cells from the basal compartment'. Together they form a unique fingerprint.

Cite this