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
  • View Affiliations

  • 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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February-2016
Volume 35 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kim B, Lee S, Park M, Seo S, Park Y, Kwon Y and Rho S: MARCKSL1 exhibits anti-angiogenic effects through suppression of VEGFR-2-dependent Akt/PDK-1/mTOR phosphorylation. Oncol Rep 35: 1041-1048, 2016
APA
Kim, B., Lee, S., Park, M., Seo, S., Park, Y., Kwon, Y., & Rho, S. (2016). MARCKSL1 exhibits anti-angiogenic effects through suppression of VEGFR-2-dependent Akt/PDK-1/mTOR phosphorylation. Oncology Reports, 35, 1041-1048. https://doi.org/10.3892/or.2015.4408
MLA
Kim, B., Lee, S., Park, M., Seo, S., Park, Y., Kwon, Y., Rho, S."MARCKSL1 exhibits anti-angiogenic effects through suppression of VEGFR-2-dependent Akt/PDK-1/mTOR phosphorylation". Oncology Reports 35.2 (2016): 1041-1048.
Chicago
Kim, B., Lee, S., Park, M., Seo, S., Park, Y., Kwon, Y., Rho, S."MARCKSL1 exhibits anti-angiogenic effects through suppression of VEGFR-2-dependent Akt/PDK-1/mTOR phosphorylation". Oncology Reports 35, no. 2 (2016): 1041-1048. https://doi.org/10.3892/or.2015.4408