Stanniocalcin1 (STC1) Inhibits Cell Proliferation and Invasion of Cervical Cancer Cells
Fengjie Guo, Yalin Li, Jiajia Wang, Yandong Li, Yuehui Li, Guancheng Li, Fengjie Guo, Yalin Li, Jiajia Wang, Yandong Li, Yuehui Li, Guancheng Li
Abstract
STC1 is a glycoprotein hormone involved in calcium/phosphate (Pi) homeostasis. There is mounting evidence that STC1 is tightly associated with the development of cancer. But the function of STC1 in cancer is not fully understood. Here, we found that STC1 is down-regulated in Clinical tissues of cervical cancer compared to the adjacent normal cervical tissues (15 cases). Subsequently, the expression of STC1 was knocked down by RNA interference in cervical cancer CaSki cells and the low expression promoted cell growth, migration and invasion. We also found that STC1 overexpression inhibited cell proliferation and invasion of cervical cancer cells. Moreover, STC1 overexpression sensitized CaSki cells to drugs. Further, we showed that NF-κB p65 protein directly bound to STC1 promoter and activated the expression of STC1 in cervical cancer cells. Thus, these results provided evidence that STC1 inhibited cell proliferation and invasion through NF-κB p65 activation in cervical cancer.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
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References
- Jiang WQ, Chang AC, Satoh M, Furuichi Y, Tam PP, et al. (2000) The distribution of stanniocalcin 1 protein in fetal mouse tissues suggests a role in bone and muscle development. J Endocrinol 165 457–466.
- Yoshiko Y, Aubin JE (2004) Stanniocalcin 1 as a pleiotropic factor in mammals. Peptides 25 1663–1669.
- Olsen HS, Cepeda MA, Zhang QQ, Rosen CA, Vozzolo BL (1996) Human stanniocalcin: a possible hormonal regulator of mineral metabolism. Proc Natl Acad Sci USA 93: 1792–1796.
- Liu G, Yang G, Chang B, Mercado-Uribe I, Huang M, et al. (2010) Stanniocalcin 1 and ovarian tumorigenesis. J Natl Cancer Inst 102: 812–827.
- Law AY, Yeung BH, Ching L, Wong CK (2011) Sp1 is a transcription repressor to stanniocalcin-1 expression in TSA-treated human colon cancer cells, HT29. J Cell Biochem 112: 2089–2096.
- Wu S, Yoshiko Y, De Luca F (2006) Stanniocalcin 1 acts as a paracrine regulator of growth plate chondrogenesis. J Biol Chem 281: 5120–5127.
- Varghese R, Gagliardi AD, Bialek PE, Yee SP, Wagner GF, et al. (2002) Overexpression of human stanniocalcin affects growth and reproduction in transgenic mice. Endocrinology 143: 868–876.
- Hasilo CP, McCudden CR, Gillespie JR, James KA, Hirvi ER, et al. (2005) Nuclear targeting of stanniocalcin to mammary gland alveolar cells during pregnancy and lactation. Am J Phsiol Endoerinol Metab 289: 634–642.
- Filvaroff EH, Guillet S, Zlot C, Bao M, Ingle G, et al. (2002) Stanniocalcin 1 alter smuscle and bone structure and function in transgenic mice. Endocrinology 143: 3681–3690.
- Zaidi D, James KA, Wagner GF (2006) Passive immunization of lactating mice with stanniocalcin-1 antiserum reduces mammary gland development, milk fat content, and postnatal pup growth. Am J Physiol Endocrinol Metab 291: E974–981.
- Chang AC, Janosi J, Hulsbeek M, de Jong D, Jeffrey KJ, et al. (1995) A novel human cDNA highly homologous to the fish hormone stanniocalcin. Mol Cell Endocrinol 112: 241–247.
- McCudde CR, Majewski A, Chakrabarti S, Wagner GF (2004) Co-localizaztion of stanniocalcin-1 ligand and receptor in human breast carcinomas. Mol Cell Endocrinol 213: 167–172.
- Fujiwara Y, Sugita Y, Nakamori S, Miyamoto A, Shiozaki K, et al. (2000) Assessment of Stanniocalcin-1 mRNA as a molecular marker for micrometastases of various human cancers. Int J Oncol 16: 799–804.
- Okabe H, Satoh S, Kato T, Kitahara O, Yanagawa R, et al. (2001) Genome-wide analysis of gene expression in human hepatocellular carcinomas using cDNA microarray: identification of genes involved in viral carcinogenesis and tumor progression. Cancer Res 61: 2129–2137.
- Macartney-Coxson DP, Hood KA, Shi HJ, Ward T, Wiles A, et al. (2008) Metastatic susceptibility locus, an 8p hot-spot for tumour progression disrupted in colorectal liver metastases: 13 candidate genes examined at the DNA, mRNA and protein level. BMC Cancer 8: 187.
- Watanabe T, Ichihara M, Hashimoto M, Shimono K, Shimoyama Y, et al. (2002) Characterization of gene expression induced by RET with MEN2A or MEN2B mutation. Am J Pathol 161: 249–256.
- Ismail RS, Baldwin RL, Fang J, Browning D, Karlan BY, et al. (2000) Differential gene expression between normal and tumor-derived ovarian epithelial cells. Cancer Res 60: 6744–6749.
- Tohmiya Y, Koide Y, Fujimaki S, Harigae H, Funato T, et al. (2004) Stanniocalcin-1 as a novel marker to detect minimal residual disease of human leukemia. Tohoku J Exp Med 204: 125–133.
- Tamura S, Oshima T, Yoshihara K, Kanazawa A, Yamada T, et al. (2011) Clinical significance of STC1 gene expression in patients with colorectal cancer. Anticancer Res 31: 325–329.
- Gerritsen ME, Soriano R, Yang S, Ingle G, Zlot C, et al. (2002) In silico data filtering to identify new angiogenesis targets from a large in vitro gene profiling data set. Physiol Genomics 10: 13–20.
- Lal A, Peters H, St Croix B, Haroon ZA, Dewhirst MW, et al. (2001) Transcriptional response to hypoxia in human tumors. J Natl Cancer Inst 93: 1337–1343.
- Law AY, Lai KP, Lui WC, Wan HT, Wong CK (2008) Histone deacetylase inhibitor-induced cellular apoptosis involves stanniocalcin-1 activation. Exp Cell Res 314: 2975–2984.
- del Campo JM, Prat A, Gil-Moreno A, Pérez J, Parera M (2008) Update on novel therapeutic agents for cervical cancer. Gynecol Oncol 110: S72–76.
- Christensen SB, Skytte DM, Denmeade SR, Dionne C, Møller JV, et al. (2009) A Trojan horse in drug development: targeting of thapsigargins towards prostate cancer cells. Anticancer Agents Med Chem 9: 276–294.
- Fels DR, Ye J, Segan AT, Kridel SJ, Spiotto M, et al. (2008) Preferential cytotoxicity of bortezomib toward hypoxic tumor cells via overactivation of endoplasmic reticulum stress pathways. Cancer Res 68: 9323–9330.
- Diaz-Padilla I, Duran I, Clarke BA, Oza AM (2012) Biologic rationale and clinical activity of mTOR inhibitors in gynecological cancer. Cancer Treat Rev 38: 767–775.
- Fukasawa M, Tsuchiya T, Takayama E, Shinomiya N, Uyeda K, et al. (2004) Identification and characterization of the hypoxia-responsive element of the human placental 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene. J Biochem. 136: 273–277.
- Thompson JS, Asmis R, Tapp AA, Nelson B, Chu Y, et al. (. 2010) Pyrrolidine dithiocarbamate (PDTC) blocks apoptosis and promotes ionizing radiation-induced necrosis of freshly-isolated normal mouse spleen cells. Apoptosis 15: 705–714.
- Chang AC, Jellinek DA, Reddel RR (2003) Mammalian stanniocalcins and cancer. Endocr Relat Cancer 10: 359–373.
- Law AY, Ching LY, Lai KP, Wong CK (2010) Identification and characterization of the hypoxia-responsive element in human stanniocalcin-1 gene. Mol Cell Endocrinol 314: 118–127.
- Chen C, Jamaluddin MS, Yan S, Sheikh-Hamad D, Yao Q (2008) Human stanniocalcin-1 blocks TNF-alpha-induced monolayer permeability in human coronary artery endothelial cells. Arterioscler Thromb Vasc Biol 28: 906–912.
- Guo F, Li Y, Liu Y, Wang J, Li G (2010) ARL6IP1 mediates cisplatin-induced apoptosis in CaSki cervical cancer cells. Oncol Rep 23: 1449–1455.
- Li X, Shen L, Zhang J, Su J, Shen L, et al. (2007) Degradation of HER2 by Cbl-based chimeric ubiquitin ligases. Cancer Res 67: 8716–8724.
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