SOX2 promotes tumorigenicity and inhibits the differentiation of I-type neuroblastoma cells

Yang,Shaobo; Zheng,Jicui; Xiao,Xianmin; Xu,Ting; Tang,Weitao; Zhu,Haitao; Yang,Lin; Zheng,Shan; Dong,Kuiran; Zhou,Guomin; Wang,Yang

doi:10.3892/ijo.2014.2713

SOX2 promotes tumorigenicity and inhibits the differentiation of I-type neuroblastoma cells

Authors:
- Shaobo Yang
- Jicui Zheng
- Xianmin Xiao
- Ting Xu
- Weitao Tang
- Haitao Zhu
- Lin Yang
- Shan Zheng
- Kuiran Dong
- Guomin Zhou
- Yang Wang
View Affiliations

Affiliations: Department of Surgery, Children's Hospital, Fudan University, Shanghai 201102, P.R. China, Department of Anatomy and Histology and Embryology, Shanghai Medical College, Fudan University, Shanghai 201102, P.R. China
Published online on: October 17, 2014 https://doi.org/10.3892/ijo.2014.2713
Pages: 317-323

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

SOX2 is a transcription factor associated with the pluripotency, proliferative potential, and self-renewing properties observed with embryonic stem cells and germ cells. SOX2 expression has been reported in several cancers and is implicated in tumorigenesis. We previously found that SOX2 expression was correlated to the clinical stage of neuroblastoma. Recently, we found that SOX2 overexpression occurs in I-type neuroblastoma cells (BE(2)-C cells). To elucidate the tumorigenic function of SOX2, we established a SOX2 overexpressed BE(2)-C cell line. SOX2 overexpressed cells showed higher tumorigenicity than control cells and exhibited decreased expression levels of marker proteins of N- or S-type cells after agent-induced differetiation. By contrast, in cells where SOX2 mRNA expression was knocked down by gene-specific siRNA, tumorigenicty was significantly decreased and the expression levels of marker proteins of N- or S-type cells were upregulated. In conclusion, our findings indicate an important function for SOX2 in promoting tumorigenicity of I-type neuroblastoma cells and in inhibiting their differentiation, suggesting that SOX2 might be a potential therapeutic target in neuroblastoma.

View Figures

View References

1	Maris JM, Hogarty MD, Bagatell R and Cohn SL: Neuroblastoma. Lancet. 369:2106–2120. 2007. View Article : Google Scholar : PubMed/NCBI
2	Cohn SL, Pearson AD, London WB, et al: The International Neuroblastoma Risk Group (INRG) classification system: an INRG Task Force report. J Clin Oncol. 27:289–297. 2009. View Article : Google Scholar : PubMed/NCBI
3	Singh SK, Clarke ID, Terasaki M, et al: Identification of a cancer stem cell in human brain tumors. Cancer Res. 63:5821–5828. 2003.PubMed/NCBI
4	Gonzalez-Sarmiento R and Perez-Losada J: Breast cancer, a stem cell disease. Curr Stem Cell Res Ther. 3:55–65. 2008. View Article : Google Scholar : PubMed/NCBI
5	Atlasi Y, Mowla SJ, Ziaee SA and Bahrami AR: OCT-4, an embryonic stem cell marker, is highly expressed in bladder cancer. Int J Cancer. 120:1598–1602. 2007. View Article : Google Scholar : PubMed/NCBI
6	Ricci-Vitiani L, Lombardi DG, Pilozzi E, et al: Identification and expansion of human colon-cancer-initiating cells. Nature. 445:111–115. 2007. View Article : Google Scholar : PubMed/NCBI
7	Ailles LE and Weissman IL: Cancer stem cells in solid tumors. Curr Opin Biotechnol. 18:460–466. 2007. View Article : Google Scholar : PubMed/NCBI
8	Komuro H, Saihara R, Shinya M, et al: Identification of side population cells (stem-like cell population) in pediatric solid tumor cell lines. J Pediatr Surg. 42:2040–2045. 2007. View Article : Google Scholar : PubMed/NCBI
9	Ross RA and Spengler BA: Human neuroblastoma stem cells. Semin Cancer Biol. 17:241–247. 2007. View Article : Google Scholar
10	Ross RA, Biedler JL and Spengler BA: A role for distinct cell types in determining malignancy in human neuroblastoma cell lines and tumors. Cancer Lett. 197:35–39. 2003. View Article : Google Scholar : PubMed/NCBI
11	Ciccarone V, Spengler BA, Meyers MB, Biedler JL and Ross RA: Phenotypic diversification in human neuroblastoma cells: expression of distinct neural crest lineages. Cancer Res. 49:219–225. 1989.PubMed/NCBI
12	Ross RA, Spengler BA, Domenech C, et al: Human neuroblastoma I-type cells are malignant neural crest stem cells. Cell Growth Differ. 6:449–456. 1995.PubMed/NCBI
13	Walton JD, Kattan DR, Thomas SK, et al: Characteristics of stem cells from human neuroblastoma cell lines and in tumors. Neoplasia. 6:838–845. 2004. View Article : Google Scholar : PubMed/NCBI
14	Sinclair AH, Berta P, Palmer MS, et al: A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature. 346:240–244. 1990. View Article : Google Scholar : PubMed/NCBI
15	Kamachi Y, Uchikawa M and Kondoh H: Pairing SOX off: with partners in the regulation of embryonic development. Trends Genet. 16:182–187. 2000. View Article : Google Scholar : PubMed/NCBI
16	Xiang R, Liao D, Cheng T, et al: Downregulation of transcription factor SOX2 in cancer stem cells suppresses growth and metastasis of lung cancer. Br J Cancer. 104:1410–1417. 2011. View Article : Google Scholar : PubMed/NCBI
17	Ji J and Zheng PS: Expression of Sox2 in human cervical carcinogenesis. Hum Pathol. 41:1438–1447. 2010. View Article : Google Scholar : PubMed/NCBI
18	Fang X, Yu W, Li L, et al: ChIP-seq and functional analysis of the SOX2 gene in colorectal cancers. OMICS. 14:369–384. 2010. View Article : Google Scholar
19	Gen Y, Yasui K, Zen Y, et al: SOX2 identified as a target gene for the amplification at 3q26 that is frequently detected in esophageal squamous cell carcinoma. Cancer Genet Cytogenet. 202:82–93. 2010. View Article : Google Scholar : PubMed/NCBI
20	Nakatsugawa M, Takahashi A, Hirohashi Y, et al: SOX2 is overexpressed in stem-like cells of human lung adenocarcinoma and augments the tumorigenicity. Lab Invest. 91:1796–1804. 2011. View Article : Google Scholar : PubMed/NCBI
21	Lu Y, Futtner C, Rock JR, et al: Evidence that SOX2 overexpression is oncogenic in the lung. PLoS One. 5:e110222010. View Article : Google Scholar : PubMed/NCBI
22	Yang S, Zheng J, Ma Y, et al: Oct4 and Sox2 are overexpressed in human neuroblastoma and inhibited by chemotherapy. Oncol Rep. 28:186–192. 2012.PubMed/NCBI
23	Melone MA, Giuliano M, Squillaro T, et al: Genes involved in regulation of stem cell properties: studies on their expression in a small cohort of neuroblastoma patients. Cancer Biol Ther. 8:1300–1306. 2009. View Article : Google Scholar : PubMed/NCBI
24	Cui H, Ma J, Ding J, et al: Bmi-1 regulates the differentiation and clonogenic self-renewal of I-type neuroblastoma cells in a concentration-dependent manner. J Biol Chem. 281:34696–34704. 2006. View Article : Google Scholar : PubMed/NCBI
25	Zheng J, Xiao X, Liu J, et al: Growth-promoting effect of environmental endocrine disruptors on human neuroblastoma SK-N-SH cells. Environ Toxicol Pharmacol. 24:189–193. 2007. View Article : Google Scholar : PubMed/NCBI
26	Visvader JE and Lindeman GJ: Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 8:755–768. 2008. View Article : Google Scholar : PubMed/NCBI
27	Hansford LM, McKee AE, Zhang L, et al: Neuroblastoma cells isolated from bone marrow metastases contain a naturally enriched tumor-initiating cell. Cancer Res. 67:11234–11243. 2007. View Article : Google Scholar : PubMed/NCBI
28	Tong QS, Zheng LD, Tang ST, et al: Expression and clinical significance of stem cell marker CD133 in human neuroblastoma. World J Pediatr. 4:58–62. 2008. View Article : Google Scholar : PubMed/NCBI
29	Jori FP, Galderisi U, Piegari E, et al: RB2/p130 ectopic gene expression in neuroblastoma stem cells: evidence of cell-fate restriction and induction of differentiation. Biochem J. 360:569–577. 2001. View Article : Google Scholar : PubMed/NCBI