Identification of a functional role for the protease-activated receptor-1 in hypoxic breast cancer cells

Antonella Naldini, Irene Filippi, Camilla Ardinghi, Antonietta Silini, Raffaella Giavazzi, Fabio Carraro

Research output: Contribution to journalArticle

Abstract

Aberrant expression of the protease-activated receptor (PAR)-1 has been associated with tumour progression. Indeed, PAR-1 expression correlates with tumour invasiveness, as well as with cancer cell survival. As the tumour microenvironment is characterised by a low oxygen tension, we decided to investigate the role of PAR-1 in cancer cells exposed to a hypoxic microenvironment. In this study we show that hypoxia enhances PAR-1 expression in MDAMB231 breast cancer cells. We next provided evidence for a novel role of PAR-1 in protecting hypoxic breast cancer against cell death, since inhibition of PAR-1 by RNA interference resulted in a decreased cell survival. Finally, we found that treatment of hypoxic MDAMB231 cells with the specific PAR-1 agonist peptide (TRAP) resulted in a significant increase of cell survival and migration. The overall results identify for the first time a functional role for PAR-1 in the cellular responses of breast cancer to a hypoxic microenvironment.

Original languageEnglish
Pages (from-to)454-460
Number of pages7
JournalEuropean Journal of Cancer
Volume45
Issue number3
DOIs
Publication statusPublished - Feb 2009

Keywords

  • Breast cancer
  • Cell survival
  • Hypoxia
  • Protease-activated receptor-1
  • Tumour microenvironment

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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