Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
Cancer Lett. 2012 Jul 28;320(2):198-204. doi: 10.1016/j.canlet.2012.02.028. Epub 2012 Mar 1.
Integrins function as cell-extracellular matrix adhesion proteins and have been implicated in tumor progression. In ovarian tumors, elevated integrin β1 expression correlates with high clinical stage and poor patient survival. In this study, we report that EGF treatment up-regulated integrin β1 mRNA and protein levels in ovarian cancer cells. Moreover, pharmacological inhibition of MEK totally abolished EGF-induced integrin β1 up-regulation and cell invasion suggesting that MAPK/ERK signaling is required for EGF-induced integrin β1 up-regulation and cell invasion. Furthermore, we found that knockdown of integrin β1 expression reduced the intrinsic invasiveness of ovarian cancer cells and the EGF-induced cell invasion. Finally, we found that overexpression of integrin β1 was sufficient to promote ovarian cancer cell invasion. This study demonstrates that integrin β1 mediates EGF-induced cell invasion in ovarian cancer.
整合素作为细胞-细胞外基质黏附蛋白,与肿瘤进展有关。在卵巢肿瘤中,整合素β1表达升高与高临床分期和患者预后不良相关。在这项研究中,我们报告表皮生长因子(EGF)处理可上调卵巢癌细胞中整合素β1 的 mRNA 和蛋白水平。此外,MEK 的药理学抑制完全消除了 EGF 诱导的整合素β1 上调和细胞侵袭,表明 MAPK/ERK 信号通路是 EGF 诱导的整合素β1 上调和细胞侵袭所必需的。此外,我们发现下调整合素β1 表达降低了卵巢癌细胞的固有侵袭性和 EGF 诱导的细胞侵袭。最后,我们发现整合素β1 的过表达足以促进卵巢癌细胞的侵袭。这项研究表明,整合素β1 介导了 EGF 诱导的卵巢癌细胞侵袭。