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.
Keywords
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Article info
Publication history
Published online: December 01, 2008
Accepted:
October 16,
2008
Received in revised form:
October 10,
2008
Received:
August 6,
2008
Identification
Copyright
© 2008 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
