c-Met signaling regulates cortactin phosphorylation and the migration and invasion of oral squamous cell carcinoma cells

• Main Authors: Ya-Wen Chiu, 邱雅雯
• Other Authors: Ta-ChunYuan
• Format: Others
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/3jujs4

碩士 === 國立東華大學 === 生命科學系 === 102 === Oral squamous cell carcinoma (OSCC) is the one of the most frequently diagnosed cancers worldwide. In Taiwan, the incidence of OSCC increases year by year due to the changes in people life style and diet. In 2013, OSCC became as the 4th leading cancer death in male Taiwanese. Previous studies show that c-Met and cortactin are highly expressed in OSCC tumors; however, their functional roles in regulating the migration and invasion of OSCC cells are mostly unknown. In current study, we initially analyzed the protein and phosphorylation levels of c-Met, FAK, PYK2, c-Src, and cortactin in three OSCC cell lines. Compared to the low-invading SCC4 and SCC25 cells, the high-invading OECM-1 cells exhibited high phosphorylation of c-Met, FAK, PYK2, c-Src, and cortactin. Knockdown of cortactin inhibited the migration and invasion of OECM-1 cells. Treatment of HGF in SCC25 cells promoted the activities of c-Met, PYK2, c-Src, and cortactin and enhanced cell migration and invasion, whereas knockdown of c-Met in OECM-1 cells caused decreases in the activities of FAK, PYK2, c-Src, and cortactin, and inhibited cell migration and invasion. Interestingly, inhibition of FAK or PYK2 activities by PF-431496 or knockdown of FAK or PYK2 expression in OECM-1 cells led to a decrease in c-Src activity but had no effect on cortactin phosphorylation. Taken together, the data clearly showed that c-Met via cortactin activation promoted the migration and invasion of OSCC cells in a FAK-independent manner. Thus, c-Met and cortactin may serve as the potential targets for developing the therapeutic strategy for the treatment of patients bearing malignant OSCC.