Deoxycholic acid (DCA) confers an intestinal phenotype on esophageal squamous epithelium via induction of the stemness-associated reprogramming factors OCT4 and SOX2

References

• Bhat S, Coleman HG, Yousef F, Johnston BT, McManus DT, Gavin AT, Murray LJ. Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study. J Natl Cancer Inst 2011; 103:1049-57; PMID:21680910; http://dx.doi.org/10.1093/jnci/djr203
   PubMedGoogle Scholar
• Hvid-Jensen F, Pedersen L, Drewes AM, Sorensen HT, Funch-Jensen P. Incidence of adenocarcinoma among patients with Barrett's esophagus. N Engl J Med 2011; 365:1375-83; PMID:21995385; http://dx.doi.org/10.1056/NEJMoa1103042
   PubMed Web of Science ®Google Scholar
• Spechler SJ. Barrett esophagus and risk of esophageal cancer: a clinical review. Jama 2013; 310:627-36; PMID:23942681; http://dx.doi.org/10.1001/jama.2013.226450
   PubMed Web of Science ®Google Scholar
• Croagh D, Phillips WA, Redvers R, Thomas RJ, Kaur P. Identification of candidate murine esophageal stem cells using a combination of cell kinetic studies and cell surface markers. Stem Cells (Dayton, Ohio) 2007; 25:313-8; PMID:17038667; http://dx.doi.org/10.1634/stemcells.2006-0421
   PubMed Web of Science ®Google Scholar
• Kalabis J, Oyama K, Okawa T, Nakagawa H, Michaylira CZ, Stairs DB, Figueiredo JL, Mahmood U, Diehl JA, Herlyn M, et al. A subpopulation of mouse esophageal basal cells has properties of stem cells with the capacity for self-renewal and lineage specification. J Clin Invest 2008; 118:3860-9; PMID:19033657
   PubMed Web of Science ®Google Scholar
• McDonald SA, Lavery D, Wright NA, Jansen M. Barrett oesophagus: lessons on its origins from the lesion itself. Nat Rev Gastroenterol Hepatol 2015; 12:50-60; PMID:25365976; http://dx.doi.org/10.1038/nrgastro.2014.181
   PubMed Web of Science ®Google Scholar
• Leedham SJ, Preston SL, McDonald SA, Elia G, Bhandari P, Poller D, Harrison R, Novelli MR, Jankowski JA, Wright NA. Individual crypt genetic heterogeneity and the origin of metaplastic glandular epithelium in human Barrett's oesophagus. Gut 2008; 57:1041-8; PMID:18305067; http://dx.doi.org/10.1136/gut.2007.143339
   PubMed Web of Science ®Google Scholar
• Sarosi G, Brown G, Jaiswal K, Feagins LA, Lee E, Crook TW, Souza RF, Zou YS, Shay JW, Spechler SJ. Bone marrow progenitor cells contribute to esophageal regeneration and metaplasia in a rat model of Barrett's esophagus. Dis Esophagus 2008; 21:43-50; PMID:NOT_FOUND
   PubMed Web of Science ®Google Scholar
• Yu WY, Slack JM, Tosh D. Conversion of columnar to stratified squamous epithelium in the developing mouse oesophagus. Dev Biol 2005; 284:157-70; PMID:15992795; http://dx.doi.org/10.1016/j.ydbio.2005.04.042
   PubMed Web of Science ®Google Scholar
• Morrow DJ, Avissar NE, Toia L, Redmond EM, Watson TJ, Jones C, Raymond DP, Litle V, Peters JH. Pathogenesis of Barrett's esophagus: Bile acids inhibit the Notch signaling pathway with induction of CDX2 gene expression in human esophageal cells. Surgery 2009; 146:714-22; PMID:19789031; http://dx.doi.org/10.1016/j.surg.2009.06.050
   PubMed Web of Science ®Google Scholar
• Xu YJ, Watanabe T, Okazaki H, Tanigawa T, Watanabe K, Tominaga K, Fujiwara Y, Oshitani N, Arakawa T. Bile Acids Induce Expression of CDx2 and MUC2 in Normal Rat Gastric Epithelial Cells via Activation of Nuclear Receptor FXR - a Possible Mechanism of Intestinal Metaplasia in the Stomach. Gastroenterology 2009; 136:A616-A.
   Google Scholar
• Masip M, Veiga A, Izpisua Belmonte JC, Simon C. Reprogramming with defined factors: from induced pluripotency to induced transdifferentiation. Mol Hum Reprod 2010; 16:856-68; PMID:20616150; http://dx.doi.org/10.1093/molehr/gaq059
   PubMed Web of Science ®Google Scholar
• Watanabe H, Ma Q, Peng S, Adelmant G, Swain D, Song W, Fox C, Francis JM, Pedamallu CS, DeLuca DS, et al. SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas. J Clinl Invest 2014; 124:1636-45; PMID:24590290; http://dx.doi.org/10.1172/JCI71545
   PubMed Web of Science ®Google Scholar
• Que J, Luo X, Schwartz RJ, Hogan BL. Multiple roles for Sox2 in the developing and adult mouse trachea. Development (Cambridge, England) 2009; 136:1899-907; PMID:19403656; http://dx.doi.org/10.1242/dev.034629
   PubMed Web of Science ®Google Scholar
• Belting HG, Wendik B, Lunde K, Leichsenring M, Mossner R, Driever W, Onichtchouk D. Pou5f1 contributes to dorsoventral patterning by positive regulation of vox and modulation of fgf8a expression. Dev Biol 2011; 356:323-36; PMID:21621531; http://dx.doi.org/10.1016/j.ydbio.2011.05.660
   PubMed Web of Science ®Google Scholar
• Zhou G, Sun YG, Wang HB, Wang WQ, Wang XW, Fang DC. Acid and bile salt up-regulate BMP4 expression in human esophageal epithelium cells. Scand J Gastroenterol 2009; 44:926-32; PMID:19488929; http://dx.doi.org/10.1080/00365520902998661
   PubMed Web of Science ®Google Scholar
• Wang X, Yang S, Zhao X, Guo H, Ling X, Wang L, Fan C, Yu J, Zhou S. OCT3 and SOX2 promote the transformation of Barrett's esophagus to adenocarcinoma by regulating the formation of tumor stem cells. Oncol Rep 2014; 31:1745-53; PMID:24481676
   PubMed Web of Science ®Google Scholar
• Clark GW, Smyrk TC, Mirvish SS, Anselmino M, Yamashita Y, Hinder RA, DeMeester TR, Birt DF. Effect of gastroduodenal juice and dietary fat on the development of Barrett's esophagus and esophageal neoplasia: an experimental rat model. Ann Surg Oncol 1994; 1:252-61; PMID:7842295; http://dx.doi.org/10.1007/BF02303531
   PubMed Web of Science ®Google Scholar
• Pham TH, Genta RM, Spechler SJ, Souza RF, Wang DH. Development and characterization of a surgical mouse model of reflux esophagitis and Barrett's esophagus. J Gastrointest Surg 2014; 18:234-40; discussion 40–1; PMID:24190247; http://dx.doi.org/10.1007/s11605-013-2386-z
   PubMed Web of Science ®Google Scholar
• Boyer LA, Lee TI, Cole MF, Johnstone SE, Levine SS, Zucker JP, Guenther MG, Kumar RM, Murray HL, Jenner RG, et al. Core transcriptional regulatory circuitry in human embryonic stem cells. Cell 2005; 122:947-56; PMID:16153702; http://dx.doi.org/10.1016/j.cell.2005.08.020
   PubMed Web of Science ®Google Scholar
• Loh YH, Wu Q, Chew JL, Vega VB, Zhang W, Chen X, Bourque G, George J, Leong B, Liu J, et al. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Nat Genet 2006; 38:431-40; PMID:16518401; http://dx.doi.org/10.1038/ng1760
   PubMed Web of Science ®Google Scholar
• Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126:663-76; PMID:16904174; http://dx.doi.org/10.1016/j.cell.2006.07.024
   PubMed Web of Science ®Google Scholar
• Vaiphei K, Sinha SK, Kochhar R. Comparative Analysis of Oct4 in Different Histological Subtypes of Esophageal Squamous Cell Carcinomas in Different Clinical Conditions. Asian Pac J Cancer Prev 2014; 15:3519-24; PMID:24870750; http://dx.doi.org/10.7314/APJCP.2014.15.8.3519
   PubMedGoogle Scholar
• Zhou X, Huang G-R, Hu P. Over-expression of Oct4 in human esophageal squamous cell carcinoma. Mol Cells 2011; 32:39-45; PMID:21547540; http://dx.doi.org/10.1007/s10059-011-2315-5
   PubMed Web of Science ®Google Scholar
• Wang Q, He W, Lu C, Wang Z, Wang J, Giercksky KE, Nesland JM, Suo Z. Oct3/4 and Sox2 Are Significantly Associated with an Unfavorable Clinical Outcome in Human Esophageal Squamous Cell Carcinoma. Anticancer Res 2009; 29:1233-41; PMID:19414369
   PubMed Web of Science ®Google Scholar
• Stoner GD, Kaighn ME, Reddel RR, Resau JH, Bowman D, Naito Z, Matsukura N, You M, Galati AJ, Harris CC. Establishment and characterization of SV40 T-antigen immortalized human esophageal epithelial cells. Cancer Res 1991; 51:365-71; PMID:1703038
   PubMed Web of Science ®Google Scholar
• Kushner JA. Development. Esophageal stem cells, where art thou? Science 2012; 337:1051-2; PMID:22936766; http://dx.doi.org/10.1126/science.1227506
   PubMed Web of Science ®Google Scholar
• Nicholson AM, Graham TA, Simpson A, Humphries A, Burch N, Rodriguez-Justo M, Novelli M, Harrison R, Wright NA, McDonald SA, et al. Barrett's metaplasia glands are clonal, contain multiple stem cells and share a common squamous progenitor. Gut 2012; 61:1380-9; PMID:22200839; http://dx.doi.org/10.1136/gutjnl-2011-301174
   PubMed Web of Science ®Google Scholar
• Krishnadath KK, Wang KK. Molecular Pathogenesis of Barrett Esophagus: Current Evidence. Gastroenterol Clin North Am 2015; 44:233-47; PMID:26021192; http://dx.doi.org/10.1016/j.gtc.2015.02.002
   PubMed Web of Science ®Google Scholar
• Kamachi Y, Uchikawa M, Kondoh H. Pairing SOX off: with partners in the regulation of embryonic development. Trends Genet 2000; 16:182-7; PMID:10729834; http://dx.doi.org/10.1016/S0168-9525(99)01955-1
   PubMed Web of Science ®Google Scholar
• Williamson KA, Hever AM, Rainger J, Rogers RC, Magee A, Fiedler Z, Keng WT, Sharkey FH, McGill N, Hill CJ, et al. Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome. Hum Mol Genet 2006; 15:1413-22; PMID:16543359; http://dx.doi.org/10.1093/hmg/ddl064
   PubMed Web of Science ®Google Scholar
• Que J, Okubo T, Goldenring JR, Nam KT, Kurotani R, Morrisey EE, Taranova O, Pevny LH, Hogan BL. Multiple dose-dependent roles for Sox2 in the patterning and differentiation of anterior foregut endoderm. Development (Cambridge, England) 2007; 134:2521-31; PMID:17522155; http://dx.doi.org/10.1242/dev.003855
   PubMed Web of Science ®Google Scholar
• Asonuma S, Imatani A, Abe Y, Koike T, Asano N, Ohara S, Shimosegawa T. The down-regulation of a HMG box gene Sox2 by exposure to acid and bile induces the progression of Barrett's esophagus. Gastroenterology 2008; 134:A437-A; PMID:NOT_FOUND; http://dx.doi.org/10.1016/S0016-5085(08)62041-7
   PubMedGoogle Scholar
• Bhardwaj Y, DeMars CJ, Achra S, Anderson M, Prasad GA, Wang KK, Urrutia RA, Buttar N. SOX2 and CDx2, Transcriptional Regulators of Early Differentation, Play a Key Role in the Development of Acid and Bile-Associated Columnar Metaplasia. Gastroenterology 2009; 136:A596-A; PMID:NOT_FOUND; http://dx.doi.org/10.1053/j.gastro.2008.09.028
   PubMedGoogle Scholar
• Silberg DG, Swain GP, Suh ER, Traber PG. Cdx1 and cdx2 expression during intestinal development. Gastroenterology 2000; 119:961-71; PMID:11040183; http://dx.doi.org/10.1053/gast.2000.18142
   PubMed Web of Science ®Google Scholar
• Mari L, Milano F, Parikh K, Straub D, Everts V, Hoeben KK, Fockens P, Buttar NS, Krishnadath KK. A pSMAD/CDX2 complex is essential for the intestinalization of epithelial metaplasia. Cell Rep 2014; 7:1197-210; PMID:24794431; http://dx.doi.org/10.1016/j.celrep.2014.03.074
   PubMed Web of Science ®Google Scholar
• Clemons NJ, Koh SY, Phillips WA. Advances in understanding the pathogenesis of Barrett's esophagus. Discov Med 2014; 17:7-14; PMID:24411696
   PubMedGoogle Scholar
• Raghoebir L, Biermann K, Buscop-van Kempen M, Wijnen RM, Tibboel D, Smits R, Rottier RJ. Disturbed balance between SOX2 and CDX2 in human vitelline duct anomalies and intestinal duplications. Virchows Archiv 2013; 462:515-22; PMID:23568430; http://dx.doi.org/10.1007/s00428-013-1405-5
   PubMed Web of Science ®Google Scholar
• Chew JL, Loh YH, Zhang W, Chen X, Tam WL, Yeap LS, Li P, Ang YS, Lim B, Robson P, et al. Reciprocal transcriptional regulation of Pou5f1 and Sox2 via the Oct4/Sox2 complex in embryonic stem cells. Mol Cell Biol 2005; 25:6031-46; PMID:15988017; http://dx.doi.org/10.1128/MCB.25.14.6031-6046.2005
   PubMed Web of Science ®Google Scholar
• Lam CS, Mistri TK, Foo YH, Sudhaharan T, Gan HT, Rodda D, Lim LH, Chou C, Robson P, Wohland T, et al. DNA-dependent Oct4-Sox2 interaction and diffusion properties characteristic of the pluripotent cell state revealed by fluorescence spectroscopy. Biochem J 2012; 448:21-33; PMID:22909387; http://dx.doi.org/10.1042/BJ20120725
   PubMed Web of Science ®Google Scholar
• Tanaka S, Kamachi Y, Tanouchi A, Hamada H, Jing N, Kondoh H. Interplay of SOX and POU factors in regulation of the Nestin gene in neural primordial cells. Mol Cell Biol 2004; 24:8834-46; PMID:15456859; http://dx.doi.org/10.1128/MCB.24.20.8834-8846.2004
   PubMed Web of Science ®Google Scholar