Histone demethylase KDM4C activates HIF1α/VEGFA signaling through the costimulatory factor STAT3 in NSCLC

Tumor development is accompanied by high hypoxia and a dense network of immature vessels. The hypoxia-inducible factor/vascular endothelial growth factor (HIF/VEGF) signaling pathway is activated in various solid tumors. It is thought that HIF/VEGF signaling activation results from intratumoral hypoxia partly. Multiple studies have reported that VEGF is a common target gene for both transcription factors STAT3 and HIF1. KDM4C has also been reported to function as a co-activation factor for HIF-1 beta/VEGF signaling activation. In this manuscript. Our results demonstrate that KDM4C promotes NSCLC tumor angiogenesis by transcriptionally activating HIF1 alpha/VEGFA signaling pathway. We also find that STAT3 functions as a costimulatory factor in this process. This pathway opens a potential therapeutic window for the treatment of NSCLC.