biostudies-literatureZhang BDepartment of Science and Technology of Guangdong ProvinceScience, Technology and Innovation Commission of Shenzhen MunicipalityGuangdong Basic and Applied Basic Research FoundationFoundation for the National Institutes of HealthDepartment of Defense Prostate Cancer Research ProgramNational Natural Science Foundation of ChinaNCI NIH HHSe175949https://www.ebi.ac.uk/biostudies/studies/S-EPMC11245161biostudies-literatureUnknown134(14)Inactivation of phosphatase and tensin homolog (PTEN) is prevalent in human prostate cancer and causes high-grade adenocarcinoma with a long latency. Cancer-associated fibroblasts (CAFs) play a pivotal role in tumor progression, but it remains elusive whether and how PTEN-deficient prostate cancers reprogram CAFs to overcome the barriers for tumor progression. Here, we report that PTEN deficiency induced Krüppel-like factor 5 (KLF5) acetylation and that interruption of KLF5 acetylation orchestrated intricate interactions between cancer cells and CAFs that enhance FGF receptor 1 (FGFR1) signaling and promote tumor growth. Deacetylated KLF5 promoted tumor cells to secrete TNF-α, which stimulated inflammatory CAFs to release FGF9. CX3CR1 inhibition blocked FGFR1 activation triggered by FGF9 aThe Journal of clinical investigationInterruption of KLF5 acetylation promotes PTEN-deficient prostate cancer progression by reprogramming cancer-associated fibroblasts.PMC112451612021QN02Y8752021A1515110051JCYJ20220530113609020,JCYJ20200109141229255,20200925174802001P30 CA138292R01 CA171189R01CA171189W81XWH-18-1-052682273079,82303045Barwick BGLiu MDu XDong JTZhou WXia SHuang QMai FLi XDing WLi YOsunkoya AOWang WChen YZhang BNi JJfalseInterruption of KLF5 acetylation promotes PTEN-deficient prostate cancer progression by reprogramming cancer-associated fibroblasts.Inactivation of phosphatase and tensin homolog (PTEN) is prevalent in human prostate cancer and causes high-grade adenocarcinoma with a long latency. Cancer-associated fibroblasts (CAFs) play a pivotal role in tumor progression, but it remains elusive whether and how PTEN-deficient prostate cancers reprogram CAFs to overcome the barriers for tumor progression. Here, we report that PTEN deficiency induced Krüppel-like factor 5 (KLF5) acetylation and that interruption of KLF5 acetylation orchestrated intricate interactions between cancer cells and CAFs that enhance FGF receptor 1 (FGFR1) signaling and promote tumor growth. Deacetylated KLF5 promoted tumor cells to secrete TNF-α, which stimulated inflammatory CAFs to release FGF9. CX3CR1 inhibition blocked FGFR1 activation triggered by FGF9 a2024-01-01T00:00:00Z2024 May2026-06-03T03:07:56.333Z2025-04-04T08:04:08.752ZS-EPMC112451613878102410.1172/JCI175949