Identification of a functional role for the protease-activated receptor-1 in hypoxic breast cancer cells
| Autor: | C Ardinghi, Antonella Naldini, Antonietta Silini, Raffaella Giavazzi, Fabio Carraro, Irene Filippi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
medicine.medical_specialty Programmed cell death Protease-activated receptor-1 Breast Neoplasms Biology Cell survival Breast cancer Cell Line Tumor Internal medicine medicine Humans Receptor PAR-1 Receptor Hypoxia Tumour microenvironment Thrombin Cancer Hypoxia-Inducible Factor 1 alpha Subunit medicine.disease Cell Hypoxia Neoplasm Proteins Protease-activated receptor-1 Hypoxia Tumour microenvironment Cell survival Breast cancer Endocrinology Oncology Cell culture Cancer cell Cancer research Female Receptors Thrombin Breast disease Signal transduction Cell Migration Assays Signal Transduction |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|