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Updated: Jun 4, 2026

Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
07:59

Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1

Published on: December 5, 2020

Akt3 controls vascular endothelial growth factor secretion and angiogenesis in ovarian cancer cells

Tiera A Liby1, Perry Spyropoulos, Haley Buff Lindner

  • 1Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.

International Journal of Cancer
|February 26, 2011
PubMed

Insights

Akt3, a protein kinase, regulates ovarian cancer growth by controlling VEGF secretion. Blocking Akt3 reduces tumor vascularization and growth, highlighting its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The PI3K/Akt pathway is frequently dysregulated in cancers, influencing cell proliferation, metabolism, survival, and motility.
  • Akt3 has a known role in endothelial cells, regulating mitochondrial biogenesis.
  • The PI3K/Akt pathway is a critical regulator in ovarian carcinoma.

Purpose of the Study:

  • To investigate the role of Akt3 in ovarian carcinoma.
  • To determine if Akt3 regulates VEGF-induced mitochondrial biogenesis in cancer cells.
  • To elucidate the mechanism by which Akt3 influences tumor growth and vascularization.

Main Methods:

  • Ovarian cancer cell lines were used.
  • Akt3 was silenced using short hairpin RNA (shRNA).
  • Tumor growth and vascularization were assessed in a xenograft mouse model.
  • VEGF expression, secretion, and localization were analyzed.
  • RCAS1 expression and its role in VEGF secretion were investigated using siRNA.

Main Results:

  • Silencing Akt3 did not significantly reduce mitochondrial gene expression in ovarian cancer cells.
  • Akt3 blockade led to smaller, less vascularized tumors in mice, correlated with reduced VEGF expression.
  • Blocking Akt3, but not Akt1, decreased VEGF secretion and caused VEGF retention in the endoplasmic reticulum.
  • Akt3 blockade down-regulated RCAS1, a Golgi protein, impacting VEGF secretion.
  • Akt3 overexpression increased RCAS1 expression and VEGF secretion.
  • RCAS1 silencing inhibited VEGF secretion.

Conclusions:

  • Akt3 plays a significant role in regulating RCAS1 and VEGF secretion in ovarian cancer cells.
  • Akt3 influences tumor growth and vascularization, partly through the regulation of RCAS1 and VEGF.
  • Targeting Akt3 may represent a viable therapeutic strategy for ovarian cancer.

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