STC2 is upregulated in hepatocellular carcinoma and promotes cell proliferation and migration in vitro
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The human glycoprotein, stanniocalcin 2 (STC2) plays multiple roles in several tumor types, however, its function and clinical significance in hepatocellular carcinoma (HCC) remain unclear. In this study, we detected STC2 expression by quantitative real-time PCR and found STC2 was upregulated in HCC tissues,correlated with tumor size and multiplicity of HCC. Ectopic expression of STC2 markedly promoted HCC cell proliferation and colony formation, while silencing of endogenous STC2resulted in a reduced cell growth by cell cycle delay in G0/G1phase. Western blot analysis demonstrated that STC2 could regulate the expression of cyclin D1 and activate extracellular signal-regulated kinase 1/2 (ERK1/2) in a dominant-positive manner. Transwell chamber assay also indicated altered patterns of STC2 expression had an important effect on cell migration. Our findings suggest that STC2 functions as a potential oncoprotein in the development and progression of HCC as well as a promising molecular target for HCC therapy. [BMB Reports 2012; 45(11): 629-634]
Abstract
The human glycoprotein, stanniocalcin 2 (STC2) plays multiple roles in several tumor types, however, its function and clinical significance in hepatocellular carcinoma (HCC) remain unclear. In this study, we detected STC2 expression by quantitative real-time PCR and found STC2 was upregulated in HCC tissues,correlated with tumor size and multiplicity of HCC. Ectopic expression of STC2 markedly promoted HCC cell proliferation and colony formation, while silencing of endogenous STC2resulted in a reduced cell growth by cell cycle delay in G0/G1phase. Western blot analysis demonstrated that STC2 could regulate the expression of cyclin D1 and activate extracellular signal-regulated kinase 1/2 (ERK1/2) in a dominant-positive manner. Transwell chamber assay also indicated altered patterns of STC2 expression had an important effect on cell migration. Our findings suggest that STC2 functions as a potential oncoprotein in the development and progression of HCC as well as a promising molecular target for HCC therapy. [BMB Reports 2012; 45(11): 629-634]
참고문헌 (27)
- Jemal, A., "Global cancer statistics", CA Cancer J. Clin., 61, pp.69~90 (2011)
- Sherman, M., "Hepatocellular carcinoma: epidemiology, risk factors, and screening", Semin. Liver Dis., 25, pp.143~154 (2005)
- Hwang, S., "Liver transplantation and conventional surgery for advanced hepatocellular carcinoma", Transpl. Int., 23, pp.723~727 (2010)
- Villanueva, A., "Targeted therapies for hepatocellular carcinoma", Gastroenterology, 140, pp.1410~1426 (2011)
- Livraghi, T., "Treatment options in hepatocellular carcinoma today", Scand. J. Surg., 100, pp.22~29 (2011)
- Zender, L., "Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach", Cell, 125, pp.1253~1267 (2006)
- Levine, A. J., "The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes", Science, 330, pp.1340~1344 (2010)
- Flik, G., "Rainbow trout corpuscles of Stannius: stanniocalcin synthesis in vitro", Am. J. Physiol., 258, pp.R1157~R1164 (1990)
- Sterba, T., "In situ detection and distribution of stanniocalcinmRNA in the corpuscles of Stannius of sockeye salmon,Oncorhynchus nerka", Mol. Cell Endocrinol., 90, pp.179~185 (1993)
- Honda, S., "Regulation by 1alpha,25-dihydroxyvitamin D(3) of expression of stanniocalcin messages in the rat kidney and ovary", FEBS Lett., 459, pp.119~122 (1999)
- Wagner, G. F., "Stanniocalcin in the seawater salmon: structure, function, and regulation", Am. J. Physiol., 274, pp.R1177~R1185 (1998)
- Ishibashi, K., "Molecular cloning of a second human stanniocalcin homologue (STC2)", Biochem. Biophys. Res. Commun., 250, pp.252~258 (1998)
- Nguyen, A., "Stanniocalcin-1 acts in a negative feedback loop in the prosurvivalERK1", 2 signaling pathway during oxidative stress, 2009, pp.28, 1982~1992
- Lai, K. P., "Induction of stanniocalcin-1 expression in apoptotic human nasopharyngeal cancer cells by p53", Biochem. Biophys. Res. Commun., 356, pp.968~975 (2007)
- Moore, E. E., "Stanniocalcin 2: characterization of the protein and its localization to human pancreatic alpha cells", Horm. Metab Res., 31, pp.406~414 (1999)
- Tamura, K., "Stanniocalcin 2 overexpression in castration-resistant prostate cancer and aggressive prostate cancer", Cancer Sci., 100, pp.914~919 (2009)
- Law, A. Y., "Stanniocalcin-2 promotes epithelial-mesenchymal transition and invasiveness in hypoxic human ovarian cancer cells", Exp. Cell Res., 316, pp.3425~3434 (2010)
- Volland, S., "Stanniocalcin 2 promotes invasion and is associated with metastatic stages in neuroblastoma", Int. J. Cancer., 125, pp.2049~2057 (2009)
- Fazio, E. N., "Stanniocalcin 2 alters PERK signalling and reduces cellular injury during cerulein induced pancreatitis in mice", BMC Cell Biol., 12, pp.17~ (2011)
- Ito D, Walker, J. R., "Characterization of stanniocalcin 2, a novel target of the mammalian unfolded protein response with cytoprotective properties", Mol. Cell Biol., 24, pp.9456~9469 (2004)
- Tarn, W. Y., "Translational control of cyclins", Cell Div., 6, pp.5~ (2011)
- Meyer, H. A., "Identification of stanniocalcin 2 as prognostic marker in renal cell carcinoma", Eur Urol., 55, pp.669~678 (2009)
- Yokobori, T., "Clinical significance of stanniocalcin 2 as a prognostic marker in gastric cancer", Ann. Surg. Oncol., 17, pp.2601~2607 (2010)
- Yamamura, J., "mRNA expression level of estrogen-inducible gene, alpha 1-antichymotrypsin, is a predictor of early tumor recurrence in patients with invasive breast cancers", Cancer Sci., 95, pp.887~892 (2004)
- Schmitz, K. J., "Activation of the ERK and AKT signalling pathway predicts poor prognosis in hepatocellular carcinoma and ERK activation in cancer tissue is associated with hepatitis C virus infection", J Hepatol., 48, pp.83~90 (2008)
- Qin, L. X., "The prognostic significance of clinical and pathological features in hepatocellular carcinoma", World J. Gastroenterol., 8, pp.193~199 (2002)
- Too, H. P., "Real time PCR quantification of GFRalpha-2 alternatively spliced isoforms in murine brain and peripheral tissues", Brain Res. Mol. Brain Res., 114, pp.146~153 (2003)