Identification of a functional role for the protease-activated receptor-1 in hypoxic breast cancer cells
Identification of a functional role for the protease-activated receptor-1 in hypoxic breast cancer cells
复制标题
DOI：
10.1016/j.ejca.2008.10.012
复制
发表时间：
2009-02-01
影响因子：
8.4
通讯作者：
Carraro, Fabio
中科院分区：
文献类型：
--
作者：
Naldini, Antonella;Filippi, Irene;Carraro, Fabio
蛋白酶激活受体（PAR）-1的异常表达与肿瘤进展相关。事实上，PAR-1表达与肿瘤侵袭性以及癌细胞存活相关。由于肿瘤微环境的特点是低氧张力，我们决定研究PAR-1在暴露于低氧微环境的癌细胞中的作用。在这项研究中，我们表明缺氧增强了MDAMB 231乳腺癌细胞中的PAR-1表达。接下来，我们提供了PAR-1在保护缺氧乳腺癌免于细胞死亡中的新作用的证据，因为通过RNA干扰抑制PAR-1导致细胞存活减少。最后，我们发现用特异性PAR-1激动剂肽（TRAP）处理缺氧的MDAMB 231细胞导致细胞存活和迁移的显著增加。总体结果首次确定了PAR-1在乳腺癌对缺氧微环境的细胞反应中的功能作用。(C)2008爱思唯尔有限公司保留所有权利。
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. (C) 2008 Elsevier Ltd. All rights reserved.