The endocrine fibroblast growth factor FGF19 promotes prostate cancer progression
Menée in vitro et in vivo, cette étude met en évidence un mécanisme par lequel le facteur de croissance des fibroblastes FGF19 favorise la progression d'un cancer de la prostate
Prostate cancer (PCa) is the most common visceral malignancy and the second leading cause of cancer deaths in US men. There is broad evidence that FGF receptors are important in PCa initiation and progression, but the contribution of particular FGFs in this disease is not fully understood. The FGF family members FGF19, FGF21 and FGF23 comprise a distinct subfamily that circulate in serum and act in an endocrine manner. These endocrine FGFs require alpha-Klotho (KL) and/or beta-Klotho (KLB), two related single-pass transmembrane proteins restricted in their tissue distribution, to act as co-receptors along with classic FGFRs to mediate potent biological activity. Here we show that FGF19 is expressed in primary and metastatic PCa tissues where it functions as an autocrine growth factor. Exogenous FGF19 promoted the growth, invasion, adhesion and colony formation of PCa cells at low ligand concentrations. FGF19 silencing in PCa cells expressing autocrine FGF19 decreased invasion and proliferation in vitro and tumor growth in vivo. Consistent with these observations, KL and/or KLB were expressed in PCa cells in vitro and in vivo, raising the possibility that additional endocrine FGFs may also exert biological effects in PCa. Our findings support the concept that therapies targeting FGFR signaling these therapies may have efficacy in PCa and they highlight FGF19 as a relevant endocrine FGF in this setting.