OCT3 and SOX2 promote the transformation of Barrett's esophagus to adenocarcinoma by regulating the formation of tumor stem cells

Wang,Xingwei; Yang,Shiming; Zhao,Xiaoyan; Guo,Hong; Ling,Xianlong; Wang,Lei; Fan,Chaoqiang; Yu,Jing; Zhou,Shiwen

doi:10.3892/or.2014.3003

OCT3 and SOX2 promote the transformation of Barrett's esophagus to adenocarcinoma by regulating the formation of tumor stem cells

Authors:
- Xingwei Wang
- Shiming Yang
- Xiaoyan Zhao
- Hong Guo
- Xianlong Ling
- Lei Wang
- Chaoqiang Fan
- Jing Yu
- Shiwen Zhou
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Affiliations: Department of Gastroenterology, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, P.R. China, National Base for Drug Clinical Trial, The Second Affiliated Hospital, Third Military Medical University, Chongqing 400037, P.R. China
Published online on: January 28, 2014 https://doi.org/10.3892/or.2014.3003
Pages: 1745-1753

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Abstract

Barrett's esophagus (BE) is a type of precancerosis and a key risk factor for esophagus adenocarcinoma (EAC). Tumor stem cells may be the source for BE transforming to EAC. Octamer transcription factor-3/4 (OCT3/4) and SOX2 are the main transcriptional controlling factors and markers of tumor stem cells. In the present study, we observed that the expressions of OCT3/4, SOX2, TCL1 and AKT1 in BE were elevated compared to normal esophagus but were decreased compared to EAC. Moreover, we isolated a few stem-like cells in OE33 cells which showed similar biological behavior to tumor stem cells. Notably, we found that downregulation of OCT3/4 expression by siRNA inhibited the ability of clone formation and invasion of OE33 cells, and decreased the formation of side population cells and slow cycle cells. Therefore, we concluded that OCT3/4 and SOX2 play a critical role in the transformation of BE to EAC by regulating the formation of tumor stem cells and the TCL1/AKT1 pathway.

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1	Brown LM, Devesa SS and Chow WH: Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age. J Natl Cancer Inst. 100:1184–1187. 2008. View Article : Google Scholar : PubMed/NCBI
2	Sharma P: Clinical practice. Barrett’s esophagus. New Engl J Med. 361:2548–2556. 2009.
3	Tsai RY: A molecular view of stem cell and cancer cell self-renewal. Int J Biochem Cell Biol. 36:684–694. 2004. View Article : Google Scholar : PubMed/NCBI
4	Kopper L and Hajdú M: Tumor stem cells. Pathol Oncol Res. 10:69–73. 2004. View Article : Google Scholar
5	Chew JL, Loh YH, Zhang W, et al: Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. Mol Cell Biol. 25:6031–6046. 2005.PubMed/NCBI
6	Okumura-Nakanishi S, Saito M, Niwa H and Ishikawa F: Oct-3/4 and Sox2 regulate Oct-3/4 gene in embryonic stem cells. J Biol Chem. 280:5307–5317. 2005. View Article : Google Scholar : PubMed/NCBI
7	Wang X, Sun Y, Xu M, Fang DC, Gao HJ and Xu JT: Oligomicroarray-based primary study of gene expression profile changes in Barrett’s esophagus. Journal of Medical Colleges of PLA. 23:251–257. 2008.
8	Rockett JC, Larkin K, Darnton SJ, Morris AG and Matthews HR: Five newly established oesophageal carcinoma cell lines: phenotypic and immunological characterization. Br J Cancer. 75:258–263. 1997. View Article : Google Scholar
9	Okamoto K, Okazawa H, Okuda A, Sakai M, Muramatsu M and Hamada H: A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells. Cell. 60:461–472. 1990. View Article : Google Scholar : PubMed/NCBI
10	Pesce M and Schöler HR: Oct-4: gatekeeper in the beginnings of mammalian development. Stem Cells. 19:271–278. 2001. View Article : Google Scholar
11	Schöler HR: the POU factors in murine development. Trends Genet. 7:323–329. 1991.
12	Weiss MA: Floppy SOX: mutual induced fit in hmg (high-mobility group) box-DNA recognition. Mol Endocrinol. 15:353–362. 2001. View Article : Google Scholar : PubMed/NCBI
13	Wegner M: From head to toes: the multiple facets of Sox proteins. Nucleic Acids Res. 27:1409–1420. 1999. View Article : Google Scholar : PubMed/NCBI
14	Boiani M and Schöler HR: Regulatory networks in embryo-derived pluripotent stem cells. Nat Rev Mol Cell Biol. 6:872–884. 2005. View Article : Google Scholar : PubMed/NCBI
15	Jin T, Branch DR, Zhang X, et al: Examination of POU homeobox gene expression in human breast cancer cells. Int J Cancer. 81:104–112. 1999.
16	Rodriguez-Pinilla SM, Sarrio D, Moreno-Bueno G, et al: Sox2: a possible driver of the basal-like phenotype in sporadic breast cancer. Mod Pathol. 20:474–481. 2007. View Article : Google Scholar : PubMed/NCBI
17	Jones TD, Ulbright TM, Eble JN and Cheng L: OCT4: a sensitive and specific biomarker for intratubular germ cell neoplasia of the testis. Clin Cancer Res. 10:8544–8547. 2004. View Article : Google Scholar : PubMed/NCBI
18	Rijlaarsdam MA, van Herk HA, Gillis AJ, et al: Specific detection of OCT3/4 isoform A/B/B1 expression in solid (germ cell) tumours and cell lines: confirmation of OCT3/4 specificity for germ cell tumours. Br J Cancer. 105:854–863. 2011. View Article : Google Scholar : PubMed/NCBI
19	Iki K and Pour PM: Expression of Oct4, a stem cell marker, in the hamster pancreatic cancer model. Pancreatology. 6:406–413. 2006. View Article : Google Scholar : PubMed/NCBI
20	Sanada Y, Yoshida K, Ohara M, Oeda M, Konishi K and 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. 32:164–170. 2006.
21	Tai MH, Chang CC, Kiupel M, Webster JD, Olson LK and Trosko JE: Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis. Carcinogenesis. 26:495–502. 2005.PubMed/NCBI
22	Ben-Porath I, Thomson MW, Carey VJ, et al: An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet. 40:499–507. 2008. View Article : Google Scholar : PubMed/NCBI
23	Karoubi G, Gugger M, Schmid R and Dutly A: OCT4 expression in human non-small cell lung cancer: implications for therapeutic intervention. Interact Cardiovasc Thorac Surg. 8:393–397. 2009. View Article : Google Scholar : PubMed/NCBI
24	Rao P, Tannir NM and Tamboli P: Expression of OCT3/4 in renal medullary carcinoma represents a potential diagnostic pitfall. Am J Surg Pathol. 36:583–588. 2012. View Article : Google Scholar : PubMed/NCBI
25	Ivanova N, Dobrin R, Lu R, et al: Dissecting self-renewal in stem cells with RNA interference. Nature. 442:533–538. 2006. View Article : Google Scholar : PubMed/NCBI
26	Pekarsky Y, Koval A, Hallas C, et al: Tcl1 enhances Akt kinase activity and mediates its nuclear translocation. Proc Natl Acad Sci USA. 97:3028–3033. 2000. View Article : Google Scholar : PubMed/NCBI
27	Watanabe S, Umehara H, Murayama K, Okabe M, Kimura T and Nakano T: Activation of Akt signaling is sufficient to maintain pluripotency in mouse and primate embryonic stem cells. Oncogene. 25:2697–2707. 2006. View Article : Google Scholar : PubMed/NCBI
28	Matoba R, Niwa H, Masui S, et al: Dissecting Oct3/4-regulated gene networks in embryonic stem cells by expression profiling. PLoS One. 1:e262006. View Article : Google Scholar : PubMed/NCBI
29	Lapidot T, Sirard C, Vormoor J, et al: A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 367:645–648. 1994. View Article : Google Scholar : PubMed/NCBI
30	Bonnet D and Dick JE: Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 3:730–737. 1997. View Article : Google Scholar : PubMed/NCBI
31	Singh SK, Hawkins C, Clarke ID, et al: Identification of human brain tumour initiating cells. Nature. 432:396–401. 2004. View Article : Google Scholar : PubMed/NCBI
32	Singh SK, Clarke ID, Hide T and Dirks PB: Cancer stem cells in nervous system tumors. Oncogene. 23:7267–7273. 2004. View Article : Google Scholar : PubMed/NCBI
33	Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ and Clarke MF: Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 100:3983–3988. 2003. View Article : Google Scholar : PubMed/NCBI
34	Collins AT, Berry PA, Hyde C, Stower MJ and Maitland NJ: Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 65:10946–10951. 2005. View Article : Google Scholar : PubMed/NCBI
35	Suetsugu A, Nagaki M, Aoki H, Motohashi T, Kunisada T and Moriwaki H: Characterization of CD133⁺ hepatocellular carcinoma cells as cancer stem/progenitor cells. Biochem Biophys Res Commun. 351:820–824. 2006.
36	O’Brien CA, Pollett A, Gallinger S and Dick JE: A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 445:106–110. 2007.PubMed/NCBI
37	Prince ME, Sivanandan R, Kaczorowski A, et al: Identification of a subpopulation of cells with cancer stem cell properties in head and neck squamous cell carcinoma. Proc Natl Acad Sci USA. 104:973–978. 2007. View Article : Google Scholar : PubMed/NCBI
38	Zhou S, Sehuetz JD, Bunting KD, et al: The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nat Med. 7:1028–1034. 2001. View Article : Google Scholar : PubMed/NCBI
39	Bunting KD: ABC transporters as phenotypic markers and functional regulators of stem cells. Stem Cells. 20:11–20. 2002. View Article : Google Scholar : PubMed/NCBI
40	Hirschmann-Jax C, Foster AE, Wulf GG, et al: A distinct ‘side population’ of cells with high drug efflux capacity in human tumor cells. Proc Natl Acad Sci USA. 101:14228–14233. 2004.
41	Szotek PP, Pieretti-Vanmarcke R, Masiakos PT, et al: Ovarian cancer side population defines cells with stem cell-like characteristics and mullerian inhibiting substance responsiveness. Proc Natl Acad Sci USA. 103:11154–11159. 2006. View Article : Google Scholar : PubMed/NCBI
42	Zhang J, Niu C, Ye L, et al: Identification of the haematopoietic stem cells niche and control of the niche size. Nature. 425:836–841. 2003. View Article : Google Scholar : PubMed/NCBI
43	Li N, Yang H, Lu L, Duan C, Zhao C and Zhao H: Comparison of the labeling efficiency of BrdU, DiI and FISH labeling techniques in bone marrow stromal cells. Brain Res. 1215:11–19. 2008. View Article : Google Scholar : PubMed/NCBI
44	Potten CS, Owen G and Booth D: Intestinal stem cells protect their genome by selective segregation of template DNA strands. J Cell Sci. 115:2381–2388. 2002.PubMed/NCBI
45	Smith GH: Label-retaining epithelial cells in mouse mammary gland divide asymmetrically and retain their template DNA strands. Development. 132:681–687. 2005. View Article : Google Scholar : PubMed/NCBI
46	Taylor G, Lehrer MS, Jensen PJ, Sun TT and Lavker RM: Involvement of follicular stem cells in forming not only the follicle but also the epidermis. Cell. 102:451–461. 2000. View Article : Google Scholar : PubMed/NCBI
47	Sun TT and Lavker RM: Corneal epithelial stem cells: past, present, and future. J Investig Dermatol Symp Proc. 9:202–207. 2004. View Article : Google Scholar : PubMed/NCBI
48	McManus MT and Sharp PA: Gene silencing in mammals by small interfering RNAs. Nat Rev Genet. 3:737–747. 2002. View Article : Google Scholar : PubMed/NCBI
49	Zhang J and Hua ZC: Targeted gene silencing by small interfering RNA-based knock-down technology. Curr Pharm Biotechnol. 5:1–7. 2004. View Article : Google Scholar : PubMed/NCBI
50	Monk M and Holding C: Human embryonic genes re-expressed in cancer cells. Oncogene. 20:8085–8091. 2001. View Article : Google Scholar : PubMed/NCBI
51	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
52	Nichols J, Zevnik B, Anastassiadis K, et al: Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell. 95:379–391. 1998. View Article : Google Scholar : PubMed/NCBI
53	Niwa H, Miyazaki J and Smith AG: Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet. 24:372–376. 2000. View Article : Google Scholar : PubMed/NCBI