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( Zong Wei Li ),( Lic Hao Zhang ),( Han Qing Li ),( Shu Hua Shan ),( Zhuo Yu Li ) 생화학분자생물학회(구 한국생화학분자생물학회) 2014 BMB Reports Vol.47 No.8
Glucose regulated protein 78 (GRP78) is frequently highlyexpressed in tumor cells, contributing to the acquisition of severalphenotypic cancer hallmarks. GRP78 expression is also positivelycorrelated with tumor metastasis, and promotes hepatocellularcarcinoma cell invasion via increasing cell motility, however, other mechanisms involving the prometastatic roles of GRP78remain to be elucidated. Here we report that forced GRP78expression promotes colon cancer cell migration and invasionthrough upregulating MMP-2, MMP-9 and especially uPAproduction. These effects of GRP78 are mediated by enhancingthe activation of β-catenin signaling. Interestingly, we identify thatGRP78 interacts with uPA both in the cells and in the culturemedium, suggesting that GRP78 protein is likely to directlyfacilitate uPA secretion via protein-protein interaction. Takentogether, our findings demonstrate for the first time that besidesstimulation of cell motility, GRP78 can act by increasingproteases production to promote tumor cell invasion.