AUTHOR=Wang Cong , Liu Ziying , Ke Yuepeng , Wang Fen TITLE=Intrinsic FGFR2 and Ectopic FGFR1 Signaling in the Prostate and Prostate Cancer JOURNAL=Frontiers in Genetics VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.00012 DOI=10.3389/fgene.2019.00012 ISSN=1664-8021 ABSTRACT=

Advanced castrate-resistant prostate cancer (CRPC) is a poorly prognostic disease currently lacking effective cure. Understanding the molecular mechanism that underlies the initiation and progression of CRPC will provide new strategies for treating this deadly disease. One candidate target is the fibroblast growth factor (FGF) signaling axis. Loss of the intrinsic FGF7/FGF10-type 2 FGF receptor (FGFR2) pathway and gain of the ectopic type 1 FGF receptor (FGFR1) pathway are associated with the progression to malignancy in prostate cancer (PCa) and many other epithelial originating lesions. Although FGFR1 and FGFR2 share similar amino acid sequences and structural domains, the two transmembrane tyrosine kinases elicit distinctive, even sometime opposite signals in cells. Recent studies have revealed that the ectopic FGFR1 signaling pathway contributes to PCa progression via multiple mechanisms, including promoting tumor angiogenesis, reprogramming cancer cell metabolism, and potentiating inflammation in the tumor microenvironment. Thus, suppression of FGFR1 signaling can be an effective novel strategy to treat CRPC.