Fig 1: Suppressing FGFR1 kinase potentiates cell growth arrest due to SREBP2 inhibition. (A–C) DU145 cells were treated with AZD4547, Fatostatin, or 100 nM AZD4547/10 μM Fatostatin for 3 days. The viable cells were stained with the CCK-8 and quantified with a plate reader. (D). FGFR kinase and SREBP2 inhibitors synergistically reduce intracellular cholesterol pools and suppress cell growth in PCa cells. FGFR1 activates SREBP2 via ERK signaling, leading to SREBP2 phosphorylation and cleavage. The activated SREBP2 is translocated to the nucleus and enhances LDLR and HMGCR expression, thereby promoting LDLR-mediated cholesterol uptake and de novo biosynthesis. FGFR1 also suppresses IDOL (an E3 ubiquitin ligase that regulates LDLR degradation) expression and hence increases LDLR accumulation, as well as the expression of two cholesterol efflux transporters, ABCA1 and ABCG1, and thereby reduces cholesterol efflux. Suppression of FGFR1 and SRPB2 synergistically reduces intracellular cholesterol pools needed for cell growth, function, and castration resistance. Created in BioRender. Ziying Liu. (2026), https://BioRender.com/zsmvv9n (accessed on 21 January. 2026). Figure created with BioRender.com. *: p < 0.05; ***: p < 0.001.