sMEK1 inhibits endothelial cell proliferation by attenuating VEGFR-2-dependent-Akt/eNOS/HIF-1 alpha signaling pathways
- 주제(키워드) sMEK1 tumor suppressor , hypoxic condition , anti-angiogenic activity , ovarian tumor , xenograft model
- 설명문(URI) http://dx.doi.org/10.18632/oncotarget.5570
- 등재 SCIE, SCOPUS
- 발행기관 IMPACT JOURNALS LLC
- 발행년도 2015
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000120162
- 본문언어 영어
- 저작권 http://dx.doi.org/10.18632/oncotarget.5570
초록/요약
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 C gamma 1 (PLC-gamma 1), 3-phosphoinositide-dependent protein kinase 1 (PDK1), endothelial nitric oxide synthetase (eNOS), and hypoxia-inducible factor 1 (HIF-1 alpha) 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 anti-angiogenic and anti-tumor agent for use in ovarian tumor.
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