title: Type 2 Fibroblast Growth Factor Receptor Signaling Preserves Stemness and Prevents Differentiation of Prostate Stem Cells from the Basal Compartment.
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.
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hamana
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030.
authors.forename: Junchen
authors.initials: J
authors.lastname: Liu
authors.affiliation: Wenzhou Medical College, Wenzhou, 325030 Zhejiang, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030.
authors.forename: Lei
authors.initials: L
authors.lastname: An
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030; Xiamen Zhongshan Hospital, Xiamen, 361004 Fujian, China.
authors.forename: Pan
authors.initials: P
authors.lastname: You
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030.
authors.forename: Julia Y F
authors.initials: JYF
authors.lastname: Chang
authors.affiliation: Baylor College of Medicine, Houston, Texas 77030.
authors.forename: Jianming
authors.initials: J
authors.lastname: Xu
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030.
authors.forename: Chengliu
authors.initials: C
authors.lastname: Jin
authors.affiliation: Xiamen Zhongshan Hospital, Xiamen, 361004 Fujian, China.
authors.forename: Zhongying
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030.
authors.forename: Wallace L
authors.initials: WL
authors.lastname: McKeehan
authors.affiliation: Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030; Wenzhou Medical College, Wenzhou, 325030 Zhejiang, China; Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M Health Science Center, College Station, Texas 77807. Electronic address: fwang@ibt.tamhsc.edu.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D010750:Phosphoproteins / Q000032:analysis; D011467:Prostate / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism*; D015398:Signal Transduction; D018874:Spheroids, Cellular; D015534:Trans-Activators / Q000032:analysis
chemical_list: D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: cell signaling; fibroblast growth factor (FGF); fibroblast growth factor receptor (FGFR); prostate; stem cell; stem cells