MARCKSL1 exhibits anti-angiogenic effects through suppression of VEGFR-2-dependent Akt/PDK-1/mTOR phosphorylation
- 주제(키워드) Akt/PDK-1/mTOR phosphorylation , Anti-angiogenic activity , Endothelial cells , MARCKSL1 , Protein-protein interaction
- 등재 SCIE, SCOPUS
- 발행기관 Spandidos Publications
- 발행년도 2016
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000123366
- 본문언어 영어
- Published As http://dx.doi.org/10.3892/or.2015.4408
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Myristoylated alanine-rich C kinase substratelike 1 (MARCKSL1) plays a pivotal role in the regulation of apoptosis and has been shown to maintain antitumor and metastasis-suppressive properties. In the present study, we examined the effects of MARCKSL1 as a novel anti-angiogenic agent on the inhibition of angiogenesis-mediated cell migration. MARCKSL1 also reduced vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cell (HUVEC) proliferation, as well as capillary-like tubular structure formation in vitro. MARCKSL1 disrupted phosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2) in ovarian tumorigenesis. In addition MARCKSL1 showed potent anti-angiogenic activity and reduced the levels of VEGF and hypoxia-inducible factor 1 (HIF-1) expression, an essential regulator of angiogenesis. Consistently, MARCKSL1 decreased VEGF induced phosphorylation of the PI3K/Akt signaling pathway components including phosphoinositide-dependent protein kinase 1 (PDK-1), mammalian target of rapamycin (mTOR), tuberous sclerosis complex 2 (TSC-2), p70 ribosomal protein S6 kinase (p70S6K), and glycogen synthase kinase 3 (GSK-3) protein. Collectively, our results provide evidence for the physiological/biological function of an endothelial cell system involved in angiogenesis through suppression of Akt/PDK-1/mTOR phosphorylation by interaction with VEGFR-2.
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