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P70S6K 1 regulation of angiogenesis through VEGF and HIF-1alpha expression

Chuan-Xiu Bian1, Zhumei Shi, Qiao Meng

  • 1Department of Pathology, Cancer Center, Nanjing Medical University, Nanjing 210029, China.

Biochemical and Biophysical Research Communications
|July 6, 2010
PubMed

Insights

The 70kDa ribosomal S6 kinase 1 (p70S6K1) drives ovarian cancer growth and angiogenesis by boosting HIF-1alpha and VEGF expression. Inhibiting p70S6K1 offers a potential therapeutic strategy for ovarian tumors.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Signaling

Background:

  • The 70kDa ribosomal S6 kinase 1 (p70S6K1) is a key regulator of cell cycle and proliferation.
  • p70S6K1 plays a role in PTEN-negative and AKT-overexpressing tumors.
  • The precise mechanism of p70S6K1 in tumor angiogenesis is not fully understood.

Purpose of the Study:

  • To investigate the role of p70S6K1 in ovarian cancer progression.
  • To elucidate the mechanism by which p70S6K1 influences tumor angiogenesis.
  • To determine if p70S6K1 inhibition can impede ovarian tumor growth.

Main Methods:

  • Utilized vector-based small interfering RNA (siRNA) to specifically inhibit p70S6K1 in ovarian cancer cells.
  • Assessed changes in VEGF protein and transcriptional expression.
  • Analyzed HIF-1alpha and HIF-1beta protein levels.
  • Evaluated tumor growth, angiogenesis, and cell proliferation in vivo and in vitro.

Main Results:

  • Knockdown of p70S6K1 significantly reduced VEGF expression and transcriptional activation via the HIF-1alpha binding site.
  • p70S6K1 siRNA specifically inhibited HIF-1alpha protein expression, but not HIF-1beta.
  • Down-regulation of p70S6K1 inhibited ovarian tumor growth, angiogenesis, and cell proliferation, correlating with decreased VEGF and HIF-1alpha levels in tumor tissues.

Conclusions:

  • p70S6K1 is essential for ovarian tumor growth and angiogenesis.
  • The signaling pathway involves p70S6K1-mediated regulation of HIF-1alpha and VEGF expression.
  • Targeting p70S6K1 represents a potential therapeutic strategy for human ovarian cancer.

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