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

Xiaowei Wu; Yu Deng; Yukun Zu; Jin Yin

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

Am J Cancer Res. 2020 Feb 1;10(2):491-506. eCollection 2020.

Authors

Xiaowei Wu¹, Yu Deng¹, Yukun Zu¹, Jin Yin²

Affiliations

¹ Department of Thoracic Surgery, Tongji Hospital, Tongji Medical Collage of Huazhong University of Science and Technology Wuhan, Hubei Province, China.
² Department of Hematopathology, Tongji Hospital, Tongji Medical Collage of Huazhong University of Science and Technology Wuhan, Hubei Province, China.

PMID: 32195022
PMCID: PMC7061751

Abstract

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-1β/VEGF signaling activation. In this manuscript. Our results demonstrate that KDM4C promotes NSCLC tumor angiogenesis by transcriptionally activating HIF1α/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.

Keywords: HIF1α; KDM4C; NSCLC; STAT3; Tumor angiogenesis.