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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
KimB.-R.SeoS.H.ParkM.S.LeeS.-H.KwonY.RhoS.B.
Ewha Authors
권영주
SCOPUS Author ID
권영주scopus
Issue Date
2015
Journal Title
Oncotarget
ISSN
1949-2553JCR Link
Citation
vol. 6, no. 31, pp. 31830 - 31843
Keywords
Anti-angiogenic activityHypoxic conditionOvarian tumorsMEK1 tumor suppressorXenograft model
Publisher
Impact Journals LLC
Indexed
SCIE; SCOPUS scopus
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
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약학대학 > 약학과 > Journal papers
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