double-stranded rna-dependent protein kinase regulates the motility of breast cancer cells双链依赖rna的蛋白激酶调节乳腺癌细胞的能动性.pdfVIP

Double-Stranded RNA-Dependent Protein Kinase Regulates the Motility of Breast Cancer Cells 1 1 1,2 1 1 1 Mei Xu , Gang Chen , Siying Wang , Mingjun Liao , Jacqueline A. Frank , Kimberly A. Bower , 3 3 1 Zhuo Zhang , Xianglin Shi , Jia Luo * 1 Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, Kentucky, United States of America, 2 Pathophysiological Department, School of Basic Medicine, Anhui Medical University, Hefei, Anhui, China, 3 Graduate Center for Toxicology, University of Kentucky College of Medicine, Lexington, Kentucky, United States of America Abstract Double-stranded RNA (dsRNA)-dependent protein kinase (PKR) is an interferon-induced protein kinase that plays a central role in the anti-viral process. Due to its pro-apoptotic and anti-proliferative action, there is an increased interest in PKR modulation as an anti-tumor strategy. PKR is overexpressed in breast cancer cells; however, the role of PKR in breast cancer cells is unclear. The expression/activity of PKR appears inversely related to the aggressiveness of breast cancer cells. The current study investigated the role of PKR in the motility/migration of breast cancer cells. The activation of PKR by a synthesized dsRNA (PIC) significantly decreased the motility of several breast cancer cell lines (BT474, MDA-MB231 and SKBR3). PIC inhibited cell migration and blocked cell membrane ruffling without affecting cell viability. PIC also induced the reorganization of the actin cytoskeleton and impaired the formation of lamellipodia. These effects of PIC were reversed by the pretreatment of a selective PKR i