ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
VEGF/VEGFR-2 upregulates EZH2 expression in lung adenocarcinoma cells and EZH2 depletion enhances the response to platinum-based and VEGFR-2-targeted therapy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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39 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
purposeTo investigate the mechanisms of regulation and role associated with enhancer of zeste homolog 2 (EZH2) expression in lung cancer cells. EXPERIMENTAL
designWe investigated the mechanisms of EZH2 expression associated with the VEGF/VEGFR-2 pathway. Furthermore, we sought to determine the role of EZH2 in response of lung adenocarcinoma to platinum-based chemotherapy, as well as the effect of EZH2 depletion on VEGFR-2-targeted therapy in lung adenocarcinoma cell lines. In addition, we characterized EZH2 expression in lung adenocarcinoma specimens and correlated it with patients' clinical characteristics.
resultsIn this study, we demonstrate that VEGF/VEGFR-2 activation induces expression of EZH2 through the upregulation of E2F3 and hypoxia-inducible factor-1α (HIF1α), and downregulated expression of miR-101. EZH2 depletion by treatment with 3-deazaneplanocin A and knockdown by siRNA decreased the expression of EZH2 and H3K27me3, increased PARP-C level, reduced cell proliferation and migration, and increased sensitivity of the cells to treatment with cisplatin and carboplatin. In addition, high EZH2 expression was associated with poor overall survival in patients who received platinum-based adjuvant therapy, but not in patients who did not receive this therapy. Furthermore, we demonstrated for the first time that the inhibition of EZH2 greatly increased the sensitivity of lung adenocarcinoma cells to the anti-VEGFR-2 drug AZD2171.
conclusionOur results suggest that the VEGF/VEGFR-2 pathway plays a role in regulation of EZH2 expression via E2F3, HIF1α, and miR-101. EZH2 depletion decreases the malignant potential of lung adenocarcinoma and sensitivity of the cells to both platinum-based and VEGFR-2-targeted therapy.
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