title: EZH2 promotes tumor progression via regulating VEGF-A/AKT signaling in non-small cell lung cancer.
abstract: 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 Ser(473)-AKT, cell proliferation, migration and metastasis were enhanced in EZH2-overexpressing A549 cells, but inhibited in parental H2087 cells with EZH2 silencing or GSK126 treatment. AKT activity was enhanced by recombinant human VEGF-165 but 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 the VEGF-A/AKT signaling pathway.
authors: Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
authors: Jian
authors: J
authors: Geng
authors: Department of Emergency, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors: Xiao
authors: X
authors: Li
authors: National Key Lab for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors: Zhanmei
authors: Z
authors: Zhou
authors: Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors: Chin-Lee
authors: CL
authors: Wu
authors: Health Management Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. Electronic address: dm42298@21cn.com.
authors: Meng
authors: M
authors: Dai
authors: National Key Lab for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. Electronic address: xiaoyanb@126.com.
authors: Xiaoyan
authors: X
authors: Bai
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D000071221:Enhancer of Zeste Homolog 2 Protein; D005260:Female; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011379:Prognosis; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D051057:Proto-Oncogene Proteins c-akt
keywords: Enhancer of Zeste Homologue 2; Non-small cell lung carcinoma; PI3K/AKT signaling; Small interfering RNA; VEGF-A