title: Glucose regulated protein 78 promotes cell invasion via regulation of uPA production and secretion in colon cancer cells.
abstract: Glucose regulated protein 78 (GRP78) is frequently highly expressed in tumor cells, contributing to the acquisition of several phenotypic cancer hallmarks. GRP78 expression is also positively correlated with tumor metastasis, and promotes hepatocellular carcinoma cell invasion via increasing cell motility, however, other mechanisms involving the prometastatic roles of GRP78 remain to be elucidated. Here we report that forced GRP78 expression promotes colon cancer cell migration and invasion through upregulating MMP-2, MMP-9 and especially uPA production. These effects of GRP78 are mediated by enhancing the activation of β-catenin signaling. Interestingly, we identify that GRP78 interacts with uPA both in the cells and in the culture medium, suggesting that GRP78 protein is likely to directly facilitate uPA secretion via protein-protein interaction. Taken together, our findings demonstrate for the first time that besides stimulation of cell motility, GRP78 can act by increasing proteases production to promote tumor cell invasion.
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, 030006, China.
authors: Zongwei
authors: Z
authors: Li
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, 030006, China.
authors: Lichao
authors: L
authors: Zhang
authors: College of Life Science, Shanxi University, Taiyuan, 030006, China.
authors: Hanqing
authors: H
authors: Li
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, 030006, China.
authors: Shuhua
authors: S
authors: Shan
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, 030006; College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors: Zhuoyu
authors: Z
authors: Li
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D019073:HT29 Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D051176:beta Catenin; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9