G9A promotes gastric cancer metastasis by upregulating ITGB3 in a SET domain-independent manner

Lei Hu, Ming-de Zang, He-xiao Wang, Bao-gui Zhang, Zhen-qiang Wang, Zhi-yuan Fan, Huo Wu, Jian-fang Li, Li-ping Su, Min Yan, Zhi-qiang Zhu, Qiu-meng Yang (+3 others)
2018 Cell Death and Disease  
Tumor metastasis is the leading cause of death in patients with advanced gastric cancer (GC). Limited therapeutic regimens are available for this condition, which is associated with a poor prognosis, and the mechanisms underlying tumor metastasis remain unclear. In the present study, increased histone methyltransferase G9A expression in GC tissues correlated with advanced stage and shorter overall survival, and in vitro and in vivo experiments revealed that G9A promoted tumor invasion and
more » ... asis. Moreover, we observed that Reg IV induced G9A via the p-ERK/p-SP1 pathway. SP1 directly binds the G9A promoter and enhances G9A expression, and upregulated G9A then forms a transcriptional activator complex with P300 and GR, thereby promoting ITGB3 expression induced by dexamethasone (DEX) and contributing to GC metastasis. However, the G9A-mediated increase in ITGB3 expression was not dependent on the SET domain and methyltransferase activity of G9A. This study demonstrates that G9A is an independent prognostic marker and promotes metastasis in GC, thus suggesting that it may be a tumor biomarker and potential therapeutic target in GC.
doi:10.1038/s41419-018-0322-6 pmid:29449539 pmcid:PMC5833452 fatcat:kom25fdve5ajdm7nw6wvqa6cum