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MARCKSL1 exhibits anti-angiogenic effects through suppression of VEGFR-2-dependent Akt/PDK-1/mTOR phosphorylation
- MARCKSL1 exhibits anti-angiogenic effects through suppression of VEGFR-2-dependent Akt/PDK-1/mTOR phosphorylation
- Kim, Boh-Ram; Lee, Seung-Hoon; Park, Mi-Sun; Seo, Seung-Hee; Park, Young-Min; Kwon, Young-Joo; Rho, Seung-Bae
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- ONCOLOGY REPORTS
- 1021-335X; 1791-2431
- vol. 35, no. 2, pp. 1041 - 1048
- MARCKSL1; anti-angiogenic activity; protein-protein interaction; Akt/PDK-1/mTOR phosphorylation; endothelial cells
- SPANDIDOS PUBL LTD
- SCI; SCIE; SCOPUS
- Myristoylated alanine-rich C kinase substrate-like 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 la (HIF-1 alpha) 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 (p7056K), and glycogen synthase kinase 3 beta (GSK-3 beta) 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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