Glucose regulated protein 78 promotes cell invasion via regulation of uPA production and secretion in colon cancer cells
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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.
Abstract
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.
참고문헌 (20)
- Li, X., "Unfolded protein response in cancer: the physician's perspective", J. Hematol. Oncol, 4, pp.8~ (2011)
- Wang, M., "Role of the unfolded protein response regulator GRP78", BiP in development, cancer, and neurological disorders, 2009, pp.11, 2307~2316
- Zhang, J., "Association of elevated GRP78 expression with increased lymph node metastasis and poor prognosis in patients with gastric cancer", Clin. Exp. Metastasis, 23, pp.401~410 (2006)
- Zheng, H. C., "Overexpression of GRP78 and GRP94 are markers for aggressive behavior and poor prognosis in gastric carcinomas", Hum. Pathol, 39, pp.1042~1049 (2008)
- Sun, Q., "Expressions of GRP78 and Bax associate with differentiation, metastasis, and apoptosis in non-small cell lung cancer", Mol. Biol. Rep, 39, pp.6753~6761 (2012)
- Fu, Y., "Glucose regulated proteins in cancer progression, drug resistance and immunotherapy", Cancer Biol. Ther, 5, pp.741~744 (2006)
- Chiu, C. C., "Glucose-regulated protein 78 regulates multiple malignant phenotypes in head and neck cancer and may serve as a molecular target of therapeutic intervention", Mol. Cancer Ther, 7, pp.2788~2797 (2008)
- Li, Z., "Cell-surface GRP78 facilitates colorectal cancer cell migration and invasion", Int. J. Biochem. Cell Biol, 45, pp.987~994 (2013)
- Xing, X., "Overexpression of glucose-regulated protein 78 in colon cancer", Clin. Chim. Acta, 364, pp.308~315 (2006)
- Mook, O. R., "The role of gelatinases in colorectal cancer progression and metastasis", Biochim. Biophys. Acta, 1705, pp.69~89 (2004)
- Hiendlmeyer, E., "Beta-catenin up-regulates the expression of the urokinase plasminogen activator in human colorectal tumors", Cancer Res, 64, pp.1209~1214 (2004)
- Blasi, F., "uPAR: a versatile signalling orchestrator", Nat. Rev. Mol. Cell Biol, 3, pp.932~943 (2002)
- Tacchini, L., "Hepatocyte growth factor signalling stimulates hypoxia inducible factor-1 (HIF-1) activity in HepG2 hepatoma cells", Carcinogenesis, 22, pp.1363~1371 (2001)
- Agarwal, A., "The AKT", I kappa B kinase pathway promotes angiogenic, Oncogene, pp.2005, 24[DOI]
- Davidson, D. J., "Kringle 5 of human plasminogen induces apoptosis of endothelial and tumor cells through surface-expressed glucose-regulated protein 78", Cancer Res, 65, pp.4663~4672 (2005)
- Su, R., "Grp78 promotes the invasion of hepatocellular carcinoma", BMC Cancer, 10, pp.20~ (2010)
- Morin, P. J., "Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC", Science, 275, pp.1787~1790 (1997)
- Li, Z., "Glucose regulated protein 78: a critical link between tumor microenvironment and cancer hallmarks", Biochim. Biophys. Acta, 1826, pp.13~22 (2012)
- Kern, J., "GRP-78 secreted by tumor cells blocks the antiangiogenic activity of bortezomib", Blood, 114, pp.3960~3967 (2009)
- Yoshioka, I., "Urinary trypsin inhibitor suppresses surgical stress-facilitated lung metastasis of murine colon 26-L5 carcinoma cells", Anticancer Res, 25, pp.815~820 (2005)