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sMEK1 inhibits endothelial cell proliferation by attenuating VEGFR-2-dependent-Akt/eNOS/HIF-1α signaling pathways
- Title
- sMEK1 inhibits endothelial cell proliferation by attenuating VEGFR-2-dependent-Akt/eNOS/HIF-1α signaling pathways
- Authors
- Kim; B.-R.; Seo; S.H.; Park; M.S.; Lee; S.-H.; Kwon; Y.; Rho; S.B.
- Ewha Authors
- 권영주
- SCOPUS Author ID
- 권영주
- Issue Date
- 2015
- Journal Title
- Oncotarget
- ISSN
- 1949-2553
- Citation
- Oncotarget vol. 6, no. 31, pp. 31830 - 31843
- Keywords
- Anti-angiogenic activity; Hypoxic condition; Ovarian tumor; sMEK1 tumor suppressor; Xenograft model
- Publisher
- Impact Journals LLC
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- The suppressor of MEK null (sMEK1) protein possesses pro-apoptotic activities. In the current study, we reveal that sMEK1 functions as a novel anti-angiogenic factor by suppressing vascular endothelial growth factor (VEGF)-induced cell proliferation, migration, and capillary-like tubular structure in vitro. In addition, sMEK1 inhibited the phosphorylation of the signaling components up- and downstream of Akt, including phospholipase Cγ1 (PLC-γ1), 3-phosphoinositide-dependent protein kinase 1 (PDK1), endothelial nitric oxide synthetase (eNOS), and hypoxia-inducible factor 1 (HIF-1α) during ovarian tumor progression via binding with vascular endothelial growth factor receptor 2 (VEGFR-2). Furthermore, sMEK1 decreased tumor vascularity and inhibited tumor growth in a xenograft human ovarian tumor model. These results supply convincing evidence that sMEK1 controls endothelial cell function and subsequent angiogenesis by suppressing VEGFR-2-mediated PI3K/Akt/eNOS signaling pathway. Taken together, our results clearly suggest that sMEK1 might be a novel antiangiogenic and anti-tumor agent for use in ovarian tumor.
- DOI
- 10.18632/oncotarget.5570
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
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sMEK1 inhibits endothelial cell proliferation by attenuating VEGFR-2-dependent-AkteNOSHIF-1α signaling pathways.pdf(1.29 MB)
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