Sex-determining region Y-related high mobility group box (SOX)-2 is overexpressed in cervical squamous cell carcinoma and contributes cervical cancer cell migration and invasion in vitro

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• 作者：Xiaohan Chang ; Jing Zhang ; Chenglin Huang ; Xiaoao Pang ; Qingshuang Luo…
• 关键词：Sex ; determining region Y ; related high mobility group box 2 ; Cervical squamous cell carcinoma ; Clinicopathologic features ; Migration ; Invasion
• 刊名：Tumor Biology
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：36
• 期：10
• 页码：7725-7733
• 全文大小：3,782 KB
• 参考文献：1.Kokka F, Bryant A, Brockbank E, Jeyarajah A. Surgical treatment of stage IA2 cervical cancer. Cochrane Database Syst Rev. 2014;5, CD010870. doi:10.-002/-4651858.?CD010870.?pub2 .PubMed
  2.Eiben GL, da Silva DM, Fausch SC, Le Poole IC, Nishimura MI, Kast WM. Cervical cancer vaccines: recent advances in HPV research. Viral Immunol. 2003;16(2):111-1. doi:10.-089/-882824033220178-6 .CrossRef PubMed
  3.Brotherton JM. Human papillomavirus vaccination: where are we now? J Paediatr Child Health. 2014. doi:10.-111/?jpc.-2627 .PubMed
  4.He L, Wu L, Su G, Wei W, Liang L, Han L, et al. The efficacy of neoadjuvant chemotherapy in different histological types of cervical cancer. Gynecol Oncol. 2014. doi:10.-016/?j.?ygyno.-014.-6.-01 .
  5.Denny L. Cervical cancer: prevention and treatment. Discov Med. 2012;14(75):125-1.PubMed
  6.Yee GP, de Souza P, Khachigian LM. Current and potential treatments for cervical cancer. Curr Cancer Drug Targets. 2013;13(2):205-0.CrossRef PubMed
  7.Liu K, Lin B, Zhao M, Yang X, Chen M, Gao A, et al. The multiple roles for Sox2 in stem cell maintenance and tumorigenesis. Cell Signal. 2013;25(5):1264-1. doi:10.-016/?j.?cellsig.-013.-2.-13 .CrossRef PubMed
  8.Lengerke C, Fehm T, Kurth R, Neubauer H, Scheble V, Muller F, et al. Expression of the embryonic stem cell marker SOX2 in early-stage breast carcinoma. BMC Cancer. 2011;11:42. doi:10.-186/-471-2407-11-42 .PubMed Central CrossRef PubMed
  9.Velcheti V, Schalper K, Yao X, Cheng H, Kocoglu M, Dhodapkar K, et al. High SOX2 levels predict better outcome in non-small cell lung carcinomas. PLoS One. 2013;8(4), e61427. doi:10.-371/?journal.?pone.-061427 .PubMed Central CrossRef PubMed
  10.Saigusa S, Tanaka K, Toiyama Y, Yokoe T, Okugawa Y, Ioue Y, et al. Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy. Ann Surg Oncol. 2009;16(12):3488-8. doi:10.-245/?s10434-009-0617-z .CrossRef PubMed
  11.Lin F, Lin P, Zhao D, Chen Y, Xiao L, Qin W, et al. Sox2 targets cyclinE, p27 and survivin to regulate androgen-independent human prostate cancer cell proliferation and apoptosis. Cell Prolif. 2012;45(3):207-6. doi:10.-111/?j.-365-2184.-012.-0812.?x .CrossRef PubMed
  12.Hutz K, Mejias-Luque R, Farsakova K, Ogris M, Krebs S, Anton M, et al. The stem cell factor SOX2 regulates the tumorigenic potential in human gastric cancer cells. Carcinogenesis. 2014;35(4):942-0. doi:10.-093/?carcin/?bgt410 .CrossRef PubMed
  13.Yang Z, Pan X, Gao A, Zhu W. Expression of Sox2 in cervical squamous cell carcinoma. J BUON. 2014;19(1):203-.PubMed
  14.Ji J, Zheng PS. Expression of Sox2 in human cervical carcinogenesis. Hum Pathol. 2010;41(10):1438-7. doi:10.-016/?j.?humpath.-009.-1.-21 .CrossRef PubMed
  15.Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet. 2009;105(2):103-.CrossRef PubMed
  16.Peirson SN, Butler JN, Foster RG. Experimental validation of novel and conventional approaches to quantitative real-time PCR data analysis. Nucleic Acids Res. 2003;31(14), e73.PubMed Central CrossRef PubMed
  17.Maliekal TT, Bajaj J, Giri V, Subramanyam D, Krishna S. The role of Notch signaling in human cervical cancer: implications for solid tumors. Oncogene. 2008;27(38):5110-. doi:10.-038/?onc.-008.-24 .CrossRef PubMed
  18.Schwarz JK, Payton JE, Rashmi R, Xiang T, Jia Y, Huettner P, et al. Pathway-specific analysis of gene expression data identifies the PI3K/Akt pathway as a novel therapeutic target in cervical cancer. Clin Cancer Res. 2012;18(5):1464-1. doi:10.-158/-078-0432.?CCR-11-2485 .PubMed Central CrossRef PubMed
  19.Xiang R, Liao D, Cheng T, Zhou H, Shi Q, Chuang TS, et al. Downregulation of transcription factor SOX2 in cancer stem cells suppresses growth and metastasis of lung cancer. Br J Cancer. 2011;104(9):1410-. doi:10.-038/?bjc.-011.-4 .PubMed Central CrossRef PubMed
  20.Han X, Fang X, Lou X, Hua D, Ding W, Foltz G, et al. Silencing SOX2 induced mesenchymal-epithelial transition and its expression predicts liver and lymph node metastasis of CRC patients. PLoS ONE. 2012;7(8), e41335. doi:10.-371/?journal.?pone.-041335 .PubMed Central CrossRef PubMed
  21.Lou X, Han X, Jin C, Tian W, Yu W, Ding D, et al. SOX2 targets fibronectin 1 to promote cell migration and invasion in ovarian cancer: new molecular leads for therapeutic intervention. OMICS. 2013;17(10):510-. doi:10.-089/?omi.-013.-058 .PubMed Central CrossRef PubMed
  22.Gen Y, Yasui K, Nishikawa T, Yoshikawa T. SOX2 promotes tumor growth of esophageal squamous cell carcinoma through the AKT/mammalian target of rapamycin complex 1 signaling pathway. Cancer Sci. 2013;104(7):810-. doi:10.-111/?cas.-2155 .CrossRef PubMed
  23.Qin W, Dong P, Ma C, Mitchelson K, Deng T, Zhang L, et al. MicroRNA-133b is a key promoter of cervical carcinoma development through the activation of the ERK a
• 作者单位：Xiaohan Chang (1)
  Jing Zhang (1)
  Chenglin Huang (1)
  Xiaoao Pang (1)
  Qingshuang Luo (1)
  Huijie Zhang (1)
  Shulan Zhang (1)
  
  1. Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, People’s Republic of China
  
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380

文摘

Sex-determining region Y-related high mobility group box 2 (SOX-2) is a key pluripotency-associated transcription factor and may be implicated in the pathogenesis of cervical squamous cell carcinoma (SCC). The aim of this study was to explore SOX-2 expression in cervical SCC tissues and to examine whether and how SOX-2 regulates the malignant behaviors of cervical SCC cells in vitro. We here found that SOX-2 expression in the examined cervical SCC tissues was higher than that in the normal cervical and cervical intraepithelial neoplasia (CIN) tissues. Higher protein level of SOX-2 (nuclear positive staining cells ?0 %) was detected in 34.9 % (29 out of 83 cases) of cervical SCC patients. We also noted that 100 % of well-differentiated and 66.7 % of moderately differentiated cervical SCCs showed lower SOX-2 expression (nuclear positive staining cells <50 %), while 58.8 % of poorly differentiated tumors had higher SOX-2 expression (P-lt;-.05). Furthermore, the migratory and invasive capabilities of SiHa cervical cancer cells were enhanced when SOX-2 was upregulated whereas suppressed when SOX-2 was downregulated. Also, the phosphorylation levels of protein kinase B (Akt) and extracellular regulated protein kinases (ERK) 1/2 were increased in SOX-2-overexpressed cancer cells but decreased in SOX-2-depleted cells. Additionally, LY294002 (Akt pathway inhibitor) or U0126 (ERK pathway inhibitor) significantly suppressed SOX-2-overexpression-induced migration and invasion in SiHa cells. Our results indicate that differentially expressed SOX-2 is associated with tumor differentiation (P-lt;-.05) and that SOX-2 contributes to the migratory and invasive behaviors of cervical SCC in vitro. Keywords Sex-determining region Y-related high mobility group box 2 Cervical squamous cell carcinoma Clinicopathologic features Migration Invasion