EZH2 promotes tumor progression via regulating VEGF-a/AKT signaling in non-small cell lung cancer
A partir de données portant sur des patients atteints d'un cancer du poumon non à petites cellules, puis menée sur des lignées cellulaires, cette étude met en évidence des mécanismes par lesquels, en régulant la voie de signalisation VEGF-A/AKT, la protéine EZH2 favorise la progression tumorale
Enhancer of Zeste Homologue 2 (EZH2) accounts for aggressiveness and unfavorable prognosis of tumor. We investigated the mechanisms and signaling pathways of EZH2 in non-small cell lung carcinoma (NSCLC) progression. Increased expression of EZH2, vascular endothelial growth factor-A (VEGF-A) and AKT phosphorylation correlated with differentiation, lymph node metastasis, size and TNM stage in NSCLC. There was a positive correlation between EZH2 and VEGF-A expression and high EZH2 expression, as an independent prognostic factor, predicted a shorter overall survival time for NSCLC patients. The expression of VEGF-A and phosphorylated Ser473-AKT, cell proliferation, migration and metastasis were enhanced in EZH2-overexpressing A549 cells, while inhibited in parental H2087 cells with EZH2 silencing or GSK126 treatment. AKT activity was enhanced by recombinant human VEGF-165 while suppressed by bevacizumab. An AKT inhibitor MK-2206 blocked VEGF-A expression and AKT phosphorylation in parental H2087 and EZH2-overexpressing A549 cells. EZH2 activity was not affected by either VEGF-A stimulation/depletion or MK-2206 inhibition. These results demonstrate that EZH2 promotes lung cancer progression via VEGF-A/AKT signaling pathway.
http://www.sciencedirect.com/science/article/pii/S0304383515000658