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Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells
09:03

Monitoring Functionality and Morphology of Vasculature Recruited by Factors Secreted by Fast-growing Tumor-generating Cells

Published on: November 23, 2014

Inhibition of endothelial cell survival and angiogenesis by protein kinase A

Semi Kim1, Manjiri Bakre, Hong Yin

  • 1University of California, San Diego Comprehensive Cancer Center, La Jolla, California 92093, USA.

The Journal of Clinical Investigation
|October 9, 2002
PubMed

Insights

Integrin alpha5beta1 promotes endothelial cell survival during angiogenesis by suppressing protein kinase A (PKA). Inhibiting this integrin or activating PKA induces apoptosis, offering a strategy to block tumor angiogenesis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Receptors for the provisional extracellular matrix (ECM) regulate angiogenesis.
  • Integrin alpha5beta1 is a key receptor involved in tumor- and growth factor-induced angiogenesis.
  • Antagonists of integrin alpha5beta1 inhibit angiogenesis and tumor growth.

Purpose of the Study:

  • To investigate the role of integrin alpha5beta1 in endothelial cell survival during angiogenesis.
  • To elucidate the mechanism by which integrin alpha5beta1 regulates endothelial cell apoptosis.
  • To explore the potential of targeting the integrin alpha5beta1-PKA pathway for anti-angiogenesis therapy.

Main Methods:

  • In vivo studies of angiogenesis.
  • Analysis of integrin alpha5beta1 signaling.
  • Assessment of protein kinase A (PKA) activity.
  • Induction of endothelial cell apoptosis via genetic or pharmacological means.

Main Results:

  • Integrin alpha5beta1 suppresses PKA activity, promoting endothelial cell survival during angiogenesis.
  • Integrin alpha5beta1 antagonists activate PKA, leading to caspase-8 activation and apoptosis.
  • Direct PKA activation by cAMP or its catalytic subunit induces endothelial cell apoptosis and inhibits angiogenesis in vivo.

Conclusions:

  • Integrin alpha5beta1 ligation during angiogenesis suppresses a PKA-dependent apoptotic program.
  • Targeting the integrin alpha5beta1-PKA pathway offers a potential therapeutic strategy for inhibiting angiogenesis.

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