Browse > Article
http://dx.doi.org/10.5483/BMBRep.2012.45.11.086

STC2 is upregulated in hepatocellular carcinoma and promotes cell proliferation and migration in vitro  

Wang, Haixiao (Department of Hepatobiliary Surgery, Wuxi People's Hospital of Nanjing Medical University)
Wu, Kuangjie (Department of Hepatobiliary Surgery, Wuxi People's Hospital of Nanjing Medical University)
Sun, Yuan (Department of Pharmacy, Huaian No. 1 People's Hospital Affiliated to Nanjing Medical University)
Li, Yandong (Chinese National Human Genome Center, Rui-Jin Hospital, Shanghai Jiaotong University School of Medicine)
Wu, Mingyu (Department of Hepatobiliary Surgery, Wuxi People's Hospital of Nanjing Medical University)
Qiao, Qian (Department of Hepatobiliary Surgery, Wuxi People's Hospital of Nanjing Medical University)
Wei, Yuanjiang (Department of Hepatobiliary Surgery, Wuxi People's Hospital of Nanjing Medical University)
Han, Ze-Guang (Chinese National Human Genome Center, Rui-Jin Hospital, Shanghai Jiaotong University School of Medicine)
Cai, Bing (Department of Hepatobiliary Surgery, Wuxi People's Hospital of Nanjing Medical University)
Publication Information
BMB Reports / v.45, no.11, 2012 , pp. 629-634 More about this Journal
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 STC2 resulted in a reduced cell growth by cell cycle delay in G0/G1 phase. 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.
Keywords
Cell migration; Cell proliferation; Hepatocellular carcinoma; Stanniocalcin 2;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E. and Forman, D. (2011) Global cancer statistics. CA Cancer J. Clin. 61, 69-90.   DOI
2 Sherman, M. (2005) Hepatocellular carcinoma: epidemiology, risk factors, and screening. Semin. Liver Dis. 25, 143-154.   DOI   ScienceOn
3 Hwang, S., Moon, D. B. and Lee, S. G. (2010) Liver transplantation and conventional surgery for advanced hepatocellular carcinoma. Transpl. Int. 23, 723-727.   DOI   ScienceOn
4 Villanueva, A. and Llovet, J. M. (2011) Targeted therapies for hepatocellular carcinoma. Gastroenterology. 140, 1410-1426.   DOI   ScienceOn
5 Livraghi, T., Makisalo, H. and Line, P. D. (2011) Treatment options in hepatocellular carcinoma today. Scand. J. Surg. 100, 22-29.   DOI
6 Zender, L., Spector, M. S., Xue, W., Flemming, P., Cordon-Cardo, C., Silke, J., Fan, S. T., Luk, J. M., Wigler, M., Hannon, G. J., Mu, D., Lucito, R., Powers, S. and Lowe, S. W. (2006) Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell 125, 1253-1267.   DOI   ScienceOn
7 Levine, A. J. and Puzio-Kuter, A. M. (2010) The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science. 330, 1340-1344.   DOI   ScienceOn
8 Flik, G., Labedz, T., Neelissen, J. A., Hanssen, R. G., Wendelaar Bonga, S. E. and Pang, P. K. (1990) Rainbow trout corpuscles of Stannius: stanniocalcin synthesis in vitro. Am. J. Physiol. 258, R1157-1164.
9 Sterba, T., Wagner, G. F., Schroedter, I. C. and Friesen, H. G. (1993) In situ detection and distribution of stanniocalcin mRNA in the corpuscles of Stannius of sockeye salmon, Oncorhynchus nerka. Mol. Cell Endocrinol. 90, 179-185.   DOI   ScienceOn
10 Honda, S., Kashiwagi, M., Ookata, K., Tojo, A. and Hirose, S. (1999) Regulation by 1alpha,25-dihydroxyvitamin D(3) of expression of stanniocalcin messages in the rat kidney and ovary. FEBS Lett. 459, 119-122.   DOI   ScienceOn
11 Wagner, G. F., Jaworski, E. M. and Haddad, M. (1998) Stanniocalcin in the seawater salmon: structure, function, and regulation. Am. J. Physiol. 274, R1177-1185.
12 Moore, E. E., Kuestner, R. E., Conklin, D. C., Whitmore, T. E., Downey, W., Buddle, M. M., Adams, R. L., Bell, L. A., Thompson, D. L., Wolf, A., Chen, L., Stamm, M. R., Grant, F. J., Lok, S., Ren, H. and De Jongh, K. S. (1999) Stanniocalcin 2: characterization of the protein and its localization to human pancreatic alpha cells. Horm. Metab Res. 31, 406-414.   DOI
13 Ishibashi, K., Miyamoto, K., Taketani, Y., Morita, K., Takeda, E., Sasaki, S. and Imai, M. (1998) Molecular cloning of a second human stanniocalcin homologue (STC2). Biochem. Biophys. Res. Commun. 250, 252-258.   DOI   ScienceOn
14 Nguyen, A., Chang, A. C. and Reddel, R. R. (2009) Stanniocalcin-1 acts in a negative feedback loop in the prosurvival ERK1/2 signaling pathway during oxidative stress. Oncogene. 28, 1982-1992.   DOI   ScienceOn
15 Lai, K. P., Law, A. Y., Yeung, H. Y., Lee, L. S., Wagner, G. F. and Wong, C. K. (2007) Induction of stanniocalcin-1 expression in apoptotic human nasopharyngeal cancer cells by p53. Biochem. Biophys. Res. Commun. 356, 968-975.   DOI   ScienceOn
16 Tamura, K., Furihata, M., Chung, S. Y., Uemura, M., Yoshioka, H., Iiyama, T., Ashida, S., Nasu, Y., Fujioka, T., Shuin, T., Nakamura, Y. and Nakagawa, H. (2009) Stanniocalcin 2 overexpression in castration-resistant prostate cancer and aggressive prostate cancer. Cancer Sci. 100, 914-919.   DOI   ScienceOn
17 Law, A. Y. and Wong, C. K. (2010) Stanniocalcin-2 promotes epithelial-mesenchymal transition and invasiveness in hypoxic human ovarian cancer cells. Exp. Cell Res. 316, 3425-3434.   DOI   ScienceOn
18 Volland, S., Kugler, W., Schweigerer, L., Wilting, J. and Becker, J. (2009) Stanniocalcin 2 promotes invasion and is associated with metastatic stages in neuroblastoma. Int. J. Cancer. 125, 2049-2057.   DOI   ScienceOn
19 Ito D, Walker, J. R., Thompson, C. S., Moroz, I., Lin, W., Veselits, M. L., Hakim, A. M., Fienberg, A. A., Thinakaran, G. (2004) Characterization of stanniocalcin 2, a novel target of the mammalian unfolded protein response with cytoprotective properties. Mol. Cell Biol. 24, 9456-9469.   DOI   ScienceOn
20 Fazio, E. N., Dimattia, G. E., Chadi, S. A., Kernohan, K. D., Pin CL. (2011) Stanniocalcin 2 alters PERK signalling and reduces cellular injury during cerulein induced pancreatitis in mice. BMC Cell Biol. 12, 17.   DOI   ScienceOn
21 Tarn, W. Y. and Lai, M. C. (2011) Translational control of cyclins. Cell Div. 6,5.   DOI   ScienceOn
22 Meyer, H. A., Tolle, A., Jung, M., Fritzsche, F. R., Haendler, B., Kristiansen, I., Gaspert, A., Johannsen, M., Jung, K. and Kristiansen, G. (2009) Identification of stanniocalcin 2 as prognostic marker in renal cell carcinoma. Eur Urol. 55, 669-678.   DOI   ScienceOn
23 Yokobori, T., Mimori, K., Ishii, H., Iwatsuki, M., Tanaka, F., Kamohara, Y., Ieta, K., Kita, Y., Doki, Y., Kuwano, H. and Mori, M. (2010) Clinical significance of stanniocalcin 2 as a prognostic marker in gastric cancer. Ann. Surg. Oncol. 17, 2601-2607.   DOI
24 Yamamura, J., Miyoshi, Y., Tamaki, Y., Taguchi, T., Iwao, K., Monden, M., Kato, K. and Noguchi, S. (2004) 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, 887-892.   DOI   ScienceOn
25 Schmitz, K. J., Wohlschlaeger, J., Lang, H., Sotiropoulos, G. C., Malago, M., Steveling, K., Reis, H., Cicinnati, V. R., Schmid, K. W. and Baba, H. A. (2008) 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, 83-90.   DOI   ScienceOn
26 Too, H. P. (2003) Real time PCR quantification of GFRalpha-2 alternatively spliced isoforms in murine brain and peripheral tissues. Brain Res. Mol. Brain Res. 114, 146-153.   DOI   ScienceOn
27 Qin, L. X. and Tang, Z. Y. (2002) The prognostic significance of clinical and pathological features in hepatocellular carcinoma. World J. Gastroenterol. 8, 193-199.   DOI