Interuption of Klf5 acetylaiton at K358 affects gene expression profiles in Pten deficient mouse prostates. Interuption of Klf5 acetylaiton at K358 affects gene expression profiles in Pten deficient mouse prostates

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. Herein, we report that PTEN deficiency induces KLF5 acetylation; and interruption of KLF5 acetylation orchestrates intricate interactions between cancer cells and CAFs that enhance FGFR1 signaling and promote tumor growth. Deacetylated KLF5 promotes tumor cells to secrete TNF-α, which stimulates inflammatory CAFs to release FGF9. CX3CR1 inhibition blocks FGFR1 activation triggered by FGF9 and sensitizes PTEN-deficient prostate cancer to AKT inhibitor capivasertib. Overall design: Differential gene expression caused by Klf5-K358R (KR) knockin in Pten-loss mouse prostates were determined by RNA-seq in anterior prostates (AP) and dorsal prostates (DP). The prostates were dissected from 16-week mice with the genotypes of PB-Cre::Pten F/F::Klf5 W/W (WW); PB-Cre::Pten F/F::Klf5 KR/W (KRW); PB-Cre::Pten F/F::Klf5 KR/KR (KRKR).