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Medical Oncology
Published in: Medical Oncology 2/2013

01-06-2013 | Original Paper

Sox2 expression predicts poor survival of hepatocellular carcinoma patients and it promotes liver cancer cell invasion by activating Slug

Authors: Chun Sun, Lu Sun, Yan Li, Xiaonan Kang, Shu Zhang, Yinkun Liu

Published in: Medical Oncology | Issue 2/2013

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Abstract

Sox2 is a major transcription factor essential to the stemness characteristics and is associated with various types of cancers. In this study, we investigated the expressions and functional roles of Sox2 in hepatocellular carcinoma (HCC). Our data show that high level of Sox2 expression correlates with metastasis and low survival rate in HCC. HCC cells overexpressing Sox2 are characterized by active epithelial-mesenchymal transition and exhibit increased ability of transwell invasion, soft agar colonization, and sphere formation. We also found Sox2 expression was correlated with the transcription activity of SLUG promoter region. These results present novel mechanistic insight into an important role of Sox2 in HCC and suggest a potential application of Sox2 in HCC prognosis and treatment.
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Literature
1.
Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917–20.PubMedCrossRef
2.
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.PubMedCrossRef
3.
Sanada Y, Yoshida K, Ohara M, Oeda M, Konishi K, Tsutani Y. Histopathologic evaluation of stepwise progression of pancreatic carcinoma with immunohistochemical analysis of gastric epithelial transcription factor SOX2: comparison of expression patterns between invasive components and cancerous or nonneoplastic intraductal components. Pancreas. 2006;32(2):164–70.PubMedCrossRef
4.
Li XL, Eishi Y, Bai YQ, Sakai H, Akiyama Y, Tani M, et al. Expression of the SRY-related HMG box protein SOX2 in human gastric carcinoma. Int J Oncol. 2004;24(2):257–63.PubMed
5.
Rodriguez-Pinilla SM, Sarrio D, Moreno-Bueno G, Rodriguez-Gil Y, Martinez MA, Hernandez L, et al. Sox2: a possible driver of the basal-like phenotype in sporadic breast cancer. Mod Pathol. 2007;20(4):474–81.PubMedCrossRef
6.
Basu-Roy U, Seo E, Ramanathapuram L, Rapp TB, Perry JA, Orkin SH, et al. Sox2 maintains self renewal of tumor-initiating cells in osteosarcomas. Oncogene. 2012;31(18):2270–82.PubMedCrossRef
7.
Fang X, Yoon JG, Li L, Yu W, Shao J, Hua D, et al. The SOX2 response program in glioblastoma multiforme: an integrated ChIP-seq, expression microarray, and microRNA analysis. BMC Genomics. 2011;12:11.PubMedCrossRef
8.
Alonso MM, Diez-Valle R, Manterola L, Rubio A, Liu D, Cortes-Santiago N, et al. Genetic and epigenetic modifications of Sox2 contribute to the invasive phenotype of malignant gliomas. PLoS ONE. 2011;6(11):e26740.PubMedCrossRef
9.
Huang P, Qiu J, Li B, Hong J, Lu C, Wang L, et al. Role of Sox2 and Oct4 in predicting survival of hepatocellular carcinoma patients after hepatectomy. Clin Biochem. 2011;44(8–9):582–9.PubMedCrossRef
10.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.PubMedCrossRef
11.
12.
Dang H, Ding W, Emerson D, Rountree CB. Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics. BMC Cancer. 2011;11:396.PubMedCrossRef
13.
Gupta PB, Chaffer CL, Weinberg RA. Cancer stem cells: mirage or reality? Nat Med. 2009;15:1010–2.PubMedCrossRef
14.
Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–15.PubMedCrossRef
15.
Peter ME. Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle. 2009;8:843–52.PubMedCrossRef
16.
Polyak K, Weinberg RA. Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer. 2009;9:265–73.PubMedCrossRef
17.
Santisteban M, Reiman JM, Asiedu MK, Behrens MD, Nassar A, Kalli KR, et al. Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells. Cancer Res. 2009;69:2887–95.PubMedCrossRef
18.
Shan J, Shen J, Liu L, Xia F, Xu C, Duan G, et al. Nanog regulates self-renewal of cancer stem cell through IGF pathway in human hepatocellular carcinoma. Hepatology. 2012;. doi:10.​1002/​hep.​25745.
19.
Li Y, Tian B, Yang J, Zhao L, Wu X, Ye SL, et al. Stepwise metastatic human hepatocellular carcinoma cell model system with multiple metastatic potentials established through consecutive in vivo selection and studies on metastatic characteristics. J Cancer Res Clin Oncol. 2004;130(8):460–8.PubMedCrossRef
20.
Sun HC, Zhang W, Qin LX, Zhang BH, Ye QH, Wang L, et al. Positive serum hepatitis B e antigen is associated with higher risk of early recurrence and poorer survival in patients after curative resection of hepatitis B-related hepatocellular carcinoma. J Hepatol. 2007;47(5):684–90.PubMedCrossRef
21.
Yang XR, Xu Y, Shi GM, Fan J, Zhou J, Ji Y, et al. Cytokeratin 10 and cytokeratin 19: predictive markers for poor prognosis in hepatocellular carcinoma patients after curative resection. Clin Cancer Res. 2008;14(12):3850–9.PubMedCrossRef
22.
23.
Jia X, Li X, Xu Y, Zhang S, Mou W, Liu Y, et al. SOX2 promotes tumorigenesis and increases the anti-apoptotic property of human prostate cancer cell. J Mol Cell Biol. 2011;3(4):230–8.PubMedCrossRef
24.
Ding W, You H, Dang H, LeBlanc F, Galicia V, Lu SC, et al. Epithelial-to-mesenchymal transition of murine liver tumor cells promotes invasion. Hepatology. 2010;52:945–53.PubMedCrossRef
25.
Fu J, Chen Y, Cao J, Luo T, Qian YW, Yang W, et al. p28GANK overexpression accelerates hepatocellular carcinoma invasiveness and metastasis via phosphoinositol 3-kinase/AKT/hypoxia-inducible factor-1α pathways. Hepatology. 2011;53:181–92.PubMedCrossRef
26.
Sun T, Sun BC, Zhao XL, Zhao N, Dong XY, Che N, et al. Promotion of tumor cell metastasis and vasculogenic mimicry by way of transcription coactivation by Bcl-2 and Twist1: a study of hepatocellular carcinoma. Hepatology. 2011;54:1690–706.PubMedCrossRef
27.
Sun T, Zhao N, Zhao XL, Gu Q, Zhang SW, Che N, et al. Expression and functional significance of Twist1 in hepatocellular carcinoma: its role in vasculogenic mimicry. Hepatology. 2010;51:545–56.PubMedCrossRef
28.
Yang MH, Chen CL, Chau GY, Chiou SH, Su CW, Chou TY, et al. Comprehensive analysis of the independent effect of twist and snail in promoting metastasis of hepatocellular carcinoma. Hepatology. 2009;50:1464–74.PubMedCrossRef
29.
Alves CC, Carneiro F, Hoefler H, Becker KF. Role of the epithelial-mesenchymal transition regulator Slug in primary human cancers. Front Biosci. 2009;14:3035–50.PubMedCrossRef
30.
Uchikado Y, Natsugoe S, Okumura H, Setoyama T, Matsumoto M, Ishigami S, et al. Slug Expression in the E-cadherin preserved tumors is related to prognosis in patients with esophageal squamous cell carcinoma. Clin Cancer Res. 2005;11(3):1174–80.PubMed
31.
Camp ER, Findlay VJ, Vaena SG, Walsh J, Lewin DN, Turner DP, et al. Slug expression enhances tumor formation in a noninvasive rectal cancer model. J Surg Res. 2011;170(1):56–63.PubMedCrossRef
32.
Shih JY, Yang PC. The EMT regulator slug and lung carcinogenesis. Carcinogenesis. 2011;32(9):1299–304.PubMedCrossRef
33.
Schoenhals M, Kassambara A, De Vos J, Hose D, Moreaux J, Klein B. Embryonic stem cell markers expression in cancers. Biochem Biophys Res Commun. 2009;383(2):157–62.PubMedCrossRef
34.
Lin T, Ding YQ, Li JM. Overexpression of Nanog protein is associated with poor prognosis in gastric adenocarcinoma. Med Oncol. 2012;29:878–85.PubMedCrossRef
35.
Zhou X, Zhou YP, Huang GR, Gong BL, Yang B, Zhang DX, et al. Expression of the stem cell marker, Nanog, in human endometrial adenocarcinoma. Int J Gynecol Pathol. 2011;30:262–70.PubMedCrossRef
36.
Yasuda H, Tanaka K, Okita Y, Araki T, Saigusa S, Toiyama Y, et al. CD133, OCT4, and NANOG in ulcerative colitis-associated colorectal cancer. Oncol Lett. 2011;2(6):1065–71.PubMed
37.
Borrull A, Ghislin S, Deshayes F, Lauriol J, Alcaide-Loridan C, Middendorp S. Nanog and Oct4 overexpression increases motility and transmigration of melanoma cells. J Cancer Res Clin Oncol. 2012;138(7):1145–54.PubMedCrossRef
Metadata
Title
Sox2 expression predicts poor survival of hepatocellular carcinoma patients and it promotes liver cancer cell invasion by activating Slug
Authors
Chun Sun
Lu Sun
Yan Li
Xiaonan Kang
Shu Zhang
Yinkun Liu
Publication date
01-06-2013
Publisher
Springer US
Published in
Medical Oncology / Issue 2/2013
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-013-0503-1

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