Suppression of VEGF expression through interruption of the HIF‑1α and Akt signaling cascade modulates the anti‑angiogenic activity of DAPK in ovarian carcinoma cells

  • Authors:
    • Sung Taek Park
    • Boh-Ram Kim
    • Sung Ho Park
    • Jeong Heon Lee
    • Eun-Ju Lee
    • Seung-Hoon Lee
    • Seung Bae Rho
  • View Affiliations

  • Published online on: December 16, 2013     https://doi.org/10.3892/or.2013.2928
  • Pages: 1021-1029
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Abstract

Death-associated protein kinase (DAPK) plays an important role in apoptosis regulation and has been shown to maintain antitumor and metastasis suppressor properties. In the present study, we investigated whether DAPK overexpression may mediate vascular endothelial growth factor (VEGF)/hypoxia-inducible factor-1α (HIF-1α) expression and angiogenic activity in the human carcinoma cell model system. VEGF plays a pivotal role in tumor angiogenesis and tumorigenesis. We found that DAPK significantly downregulated VEGF-induced endothelial cell proliferation, migration and tube formation as well as VEGF receptor-2 (VEGFR-2) phosphorylation in vitro. In addition, DAPK exhibited potent anti-angiogenic activity and clearly decreased the levels of VEGF and HIF-1α expression, a key regulator for angiogenesis. Notably, our results strongly indicated that DAPK can disturb VEGFR-2 transcriptional activity by inhibiting VEGFR-2 phosphorylation through the PI3K/Akt signaling cascade. Collectively, our study identified a novel function of DAPK in regulating cellular VEGF/HIF-1α activity during tumorigenesis, which may act together with its anti-angiogenic function to inhibit tumor progression.
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2014-February
Volume 31 Issue 2

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

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Spandidos Publications style
Park ST, Kim B, Park SH, Lee JH, Lee E, Lee S and Rho SB: Suppression of VEGF expression through interruption of the HIF‑1α and Akt signaling cascade modulates the anti‑angiogenic activity of DAPK in ovarian carcinoma cells. Oncol Rep 31: 1021-1029, 2014
APA
Park, S.T., Kim, B., Park, S.H., Lee, J.H., Lee, E., Lee, S., & Rho, S.B. (2014). Suppression of VEGF expression through interruption of the HIF‑1α and Akt signaling cascade modulates the anti‑angiogenic activity of DAPK in ovarian carcinoma cells. Oncology Reports, 31, 1021-1029. https://doi.org/10.3892/or.2013.2928
MLA
Park, S. T., Kim, B., Park, S. H., Lee, J. H., Lee, E., Lee, S., Rho, S. B."Suppression of VEGF expression through interruption of the HIF‑1α and Akt signaling cascade modulates the anti‑angiogenic activity of DAPK in ovarian carcinoma cells". Oncology Reports 31.2 (2014): 1021-1029.
Chicago
Park, S. T., Kim, B., Park, S. H., Lee, J. H., Lee, E., Lee, S., Rho, S. B."Suppression of VEGF expression through interruption of the HIF‑1α and Akt signaling cascade modulates the anti‑angiogenic activity of DAPK in ovarian carcinoma cells". Oncology Reports 31, no. 2 (2014): 1021-1029. https://doi.org/10.3892/or.2013.2928