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Integrin alpha 7 interacts with high temperature requirement A2 (HtrA2) to induce prostate cancer cell death

Ze-Hua Zhu1, Yan P Yu, Zhong-Liang Zheng

  • 1Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

The American Journal of Pathology
|July 24, 2010
PubMed

Insights

Integrin alpha7 (ITGA7) expression triggers programmed cell death in prostate cancer cells by activating the HtrA2 protease. This interaction reveals ITGA7

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Integrins are crucial for tissue development.
  • Integrin alpha7 (ITGA7) is often downregulated in various cancers, including prostate cancer.
  • The precise role of ITGA7 in cancer suppression requires further elucidation.

Purpose of the Study:

  • To investigate the mechanism by which ITGA7 influences cancer cell viability.
  • To identify interacting partners of ITGA7 involved in cell death pathways.
  • To explore the therapeutic potential of ITGA7 in prostate cancer.

Main Methods:

  • Yeast two-hybrid analysis to identify ITGA7 interacting proteins.
  • In vitro and in vivo assays to measure HtrA2 protease activity.
  • Cell viability assays following ITGA7 expression and HtrA2 manipulation.
  • RNA interference to deplete laminin beta2.

Main Results:

  • ITGA7 expression induced apoptosis in human prostate cancer cell lines (PC3 and DU145).
  • ITGA7 directly interacts with high temperature requirement A2 (HtrA2), enhancing its protease activity.
  • Disruption of the ITGA7-HtrA2 interaction or HtrA2 function abrogated ITGA7-mediated cell death.
  • Laminin beta2 depletion exacerbated ITGA7-induced apoptosis.

Conclusions:

  • ITGA7 functions as a tumor suppressor by engaging the HtrA2 apoptotic pathway.
  • The interaction between ITGA7 and HtrA2 represents a novel mechanism for inducing cancer cell death.
  • Targeting the ITGA7-HtrA2 axis may offer a new therapeutic strategy for prostate cancer.

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