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

doi:10.3892/or.2015.4408

MARCKSL1 exhibits anti-angiogenic effects through suppression of VEGFR-2-dependent Akt/PDK-1/mTOR phosphorylation

Authors:
- Boh-Ram Kim
- Seung-Hoon Lee
- Mi-Sun Park
- Seung-Hee Seo
- Young-Min Park
- Young-Joo Kwon
- Seung-Bae Rho
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Affiliations: Research Institute, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do 410‑769, Republic of Korea, Department of Life Science, Yong In University, Cheoin-gu, Yongin-si, Gyeonggi‑do 449‑714, Republic of Korea, Department of Biological Sciences, Sungkyunkwan University, Jangan-gu, Suwon‑si, Gyeonggi‑do 440‑746, Republic of Korea, College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Global Top 5 Program, Ewha Womans University, Seoul 120-750, Republic of Korea
Published online on: November 10, 2015 https://doi.org/10.3892/or.2015.4408
Pages: 1041-1048

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Abstract

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 1α (HIF-1α) 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 3β (GSK-3β) 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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