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Background  KLF5 is a basic transcriptional factor that regulates multiple physiopathological processes. Our recent study showed that deletion of  Klf5  in mouse prostate promotes tumorigenesis initiated by the deletion of  Pten . While molecular characterization of  Klf5 -null tumors suggested that angiogenesis was partially responsible for tumor promotion, the precise function and mechanism of  KLF5  deletion in prostate tumor angiogenesis remain unclear.    Results  Applying histological staining to  Pten -null mouse prostates, we observed that deletion of  Klf5  significantly increased the number of microvessels, accompanied by the upregulation of multiple angiogenesis-related genes based on microarray analysis with MetaCore software. In human umbilical vein endothelial cells (HuVECs), tube formation and migration, both of which are indicators of angiogenic activities, were decreased by conditioned media from PC-3 and DU 145 human prostate cancer cells with  KLF5  overexpression, but increased by media from cells with  KLF5  knockdown. HIF1α, a key angiogenesis inducer, was upregulated by KLF5 loss at the protein but not the mRNA level in both mouse tissues and human cell lines, as determined by immunohistochemical staining, real-time RT-PCR and Western blotting. Consistently, KLF5 loss also upregulated VEGF and PDGF, two pro-angiogenic mediators of HIF1α function, as analyzed by immunohistochemical staining in mouse tissues and ELISA in conditioned media. Mechanistically, AKT activity, which caused the accumulation of HIF1α, was increased by  KLF5  knockout or knockdown but decreased by  KLF5  overexpression. PI3K/AKT inhibitors consistently abolished the effects of  KLF5  knockdown on angiogenic activity, HIF1α accumulation, and VEGF and PDGF expression.    Conclusion  KLF5 loss enhances tumor angiogenesis by attenuating PI3K/AKT signaling and subsequent accumulation of HIF1α in  PTEN  deficient prostate tumors.    Electronic supplementary material  The online version of this article (doi:10.1186/s12943-015-0365-6) contains supplementary material, which is available to authorized users.

KLF5 inhibits angiogenesis in PTEN-deficient prostate cancer by attenuating AKT activation and subsequent HIF1α accumulation