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Gene Review

CDX1  -  caudal type homeobox 1

Homo sapiens

Synonyms: Caudal-type homeobox protein 1, Homeobox protein CDX-1
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Disease relevance of CDX1


Psychiatry related information on CDX1


High impact information on CDX1

  • CONCLUSIONS: CDX1 may be important in the transition from normal gastric and esophageal epithelium to intestinal-type metaplasia [6].
  • The variability in expression of CDX1 in gastric and esophageal adenocarcinomas suggests more than one pathway in the development of these carcinomas [6].
  • CDX1 protein expression in normal, metaplastic, and neoplastic human alimentary tract epithelium [6].
  • The decrease of CDX1 in colonic adenocarcinomas may indicate a role for CDX1 in growth regulation and in the maintenance of the differentiated phenotype [6].
  • BACKGROUND & AIMS: CDX1 is an intestine-specific transcription factor expressed early in intestinal development that may be involved in regulation of proliferation and differentiation of intestinal epithelial cells [6].

Chemical compound and disease context of CDX1

  • Combined Bisulfite Restriction Analysis (COBRA) and bisulfite sequencing analysis revealed that the CDX1 promoter is methylated in CDX1 non-expressing colorectal cancer cell lines but not in human normal colon tissue and T84 cells, which express CDX1 [7].
  • CONCLUSIONS: The expression of CDX2 precedes those of CDX1, sucrase-isomaltase, other intestine-specific genes (human defensin-5, alkaline phosphatase), and MUC2 during the progression of intestinal metaplasia [8].

Biological context of CDX1


Anatomical context of CDX1


Associations of CDX1 with chemical compounds

  • The five remaining cell lines had a partially methylated CDX1 promoter and all expressed CDX1 mRNA; when treated with the demethylating agent, 5-aza-2'-deoxycytidine, these five cell lines all showed increased CDX1 expression [10].
  • To identify the transcriptional activator that regulates goblet-specific expression of MUC2, we analyzed the interaction between the MUC2 promoter and homeodomain proteins CDX1/2, which are involved in the regulation of intestinal development and differentiation [12].
  • CDX1 interacting with TBP is connected to members of the TFIID and Mediator complexes, two major elements of the general transcriptional machinery [13].
  • In cells overexpressing Cdx1 or Cdx2, tumorigenicity and resistance to apoptosis induced by serum starvation, ceramide, or staurosporine were not changed compared with control cells; yet phorbol ester-stimulated cell migration was decreased by 50% [14].
  • Finally, compared to control cells, Cdx1-overexpressing cells were more resistant to adriamycin-induced apoptosis, probably because they do not show concomitant decrease in endogenous Bcl-2 level [15].

Regulatory relationships of CDX1

  • It is noteworthy that CDX2 was expressed in the antral and fundic mucosa in the absence of the expression of CDX1 and gene markers for intestinal metaplasia [8].
  • Using a transfection approach, we showed here that the oncogenic activation of the beta-catenin pathway stimulates the endogenous expression of the Cdx1 mRNA as well as the activity of the Cdx1 promoter in cancer cells of the human colon [16].

Other interactions of CDX1

  • The caudal-type homeodomain transcription factors 1 (CDX1) and 2 (CDX2) regulate axial development and intestinal differentiation [1].
  • Conjugated bile salts and the inflammatory cytokines TNF-alpha and IL-1beta were all found to increase CDX1 mRNA expression in vitro [4].
  • This down-regulation was correlated with the decrease of Cdx1 and HNF1beta expression in cancer tissue [17].
  • It is not dependent on canonical CDX binding sites in the Cdx1 promoter nor on the cis-elements specifically targeted by the beta-catenin/Tcf complex [16].
  • Functional analysis revealed that Cdx1 transactivates (fourfold, P < 0.05) the IAP promoter through a novel Cdx response element (GTTTAGA) located between -2369 and -2375 upstream of the translational start site [18].

Analytical, diagnostic and therapeutic context of CDX1


  1. Expression of the caudal-type homeodomain transcription factors CDX 1/2 and outcome in carcinomas of the ampulla of Vater. Hansel, D.E., Maitra, A., Lin, J.W., Goggins, M., Argani, P., Yeo, C.J., Piantadosi, S., Leach, S.D., Biankin, A.V. J. Clin. Oncol. (2005) [Pubmed]
  2. Aberrant expression of CDX2 in Barrett's epithelium and inflammatory esophageal mucosa. Eda, A., Osawa, H., Satoh, K., Yanaka, I., Kihira, K., Ishino, Y., Mutoh, H., Sugano, K. J. Gastroenterol. (2003) [Pubmed]
  3. Relationships between the expressions of CDX1 and CDX2 mRNA and clinicopathologic features in colorectal cancers. Kim, G.H., Lee, D.H., Kim, H.W., Cheong, J.Y., Seo, S.B., Heo, J., Kang, D.H., Song, G.A., Cho, M., Yang, U.S., Park, d.o. .Y., Yoo, M.A. Korean J. Intern. Med. (2005) [Pubmed]
  4. CDX1 is an important molecular mediator of Barrett's metaplasia. Wong, N.A., Wilding, J., Bartlett, S., Liu, Y., Warren, B.F., Piris, J., Maynard, N., Marshall, R., Bodmer, W.F. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  5. Isolation, characterization, and precise physical localization of human CDX1, a caudal-type homeobox gene. Bonner, C.A., Loftus, S.K., Wasmuth, J.J. Genomics (1995) [Pubmed]
  6. CDX1 protein expression in normal, metaplastic, and neoplastic human alimentary tract epithelium. Silberg, D.G., Furth, E.E., Taylor, J.K., Schuck, T., Chiou, T., Traber, P.G. Gastroenterology (1997) [Pubmed]
  7. DNA methylation down-regulates CDX1 gene expression in colorectal cancer cell lines. Suh, E.R., Ha, C.S., Rankin, E.B., Toyota, M., Traber, P.G. J. Biol. Chem. (2002) [Pubmed]
  8. Expression of homeobox gene CDX2 precedes that of CDX1 during the progression of intestinal metaplasia. Eda, A., Osawa, H., Yanaka, I., Satoh, K., Mutoh, H., Kihira, K., Sugano, K. J. Gastroenterol. (2002) [Pubmed]
  9. The caudal-related homeodomain protein CDX1 activates proliferating cell nuclear antigen expression in hepatocellular and colorectal carcinoma cells. Oh, E.J., Park, J.H., Cho, M., Lee, W.J., Choi, Y.H., Yoo, M.A. Int. J. Oncol. (2002) [Pubmed]
  10. Loss of CDX1 expression in colorectal carcinoma: promoter methylation, mutation, and loss of heterozygosity analyses of 37 cell lines. Wong, N.A., Britton, M.P., Choi, G.S., Stanton, T.K., Bicknell, D.C., Wilding, J.L., Bodmer, W.F. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  11. Putative intestine-specific enhancers located in 5' sequence of the CDX1 gene regulate CDX1 expression in the intestine. Rankin, E.B., Xu, W., Silberg, D.G., Suh, E. Am. J. Physiol. Gastrointest. Liver Physiol. (2004) [Pubmed]
  12. Homeodomain protein CDX2 regulates goblet-specific MUC2 gene expression. Yamamoto, H., Bai, Y.Q., Yuasa, Y. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  13. Functional interaction between the homeoprotein CDX1 and the transcriptional machinery containing the TATA-binding protein. Calon, A., Gross, I., Davidson, I., Kedinger, M., Duluc, I., Domon-Dell, C., Freund, J.N. Nucleic Acids Res. (2007) [Pubmed]
  14. Expression of the Cdx1 and Cdx2 homeotic genes leads to reduced malignancy in colon cancer-derived cells. Mallo, G.V., Soubeyran, P., Lissitzky, J.C., André, F., Farnarier, C., Marvaldi, J., Dagorn, J.C., Iovanna, J.L. J. Biol. Chem. (1998) [Pubmed]
  15. The homeobox gene Cdx1 belongs to the p53-p21(WAF)-Bcl-2 network in intestinal epithelial cells. Moucadel, V., Totaro, M.S., Dell, C.D., Soubeyran, P., Dagorn, J.C., Freund, J.N., Iovanna, J.L. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  16. Stimulation of Cdx1 by oncogenic beta-catenin/Tcf4 in colon cancer cells; opposite effect of the CDX2 homeoprotein. Domon-Dell, C., Freund, J.N. FEBS Lett. (2002) [Pubmed]
  17. Lewis type 1 antigen synthase (beta3Gal-T5) is transcriptionally regulated by homeoproteins. Isshiki, S., Kudo, T., Nishihara, S., Ikehara, Y., Togayachi, A., Furuya, A., Shitara, K., Kubota, T., Watanabe, M., Kitajima, M., Narimatsu, H. J. Biol. Chem. (2003) [Pubmed]
  18. Differential regulation of intestinal alkaline phosphatase gene expression by Cdx1 and Cdx2. Alkhoury, F., Malo, M.S., Mozumder, M., Mostafa, G., Hodin, R.A. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  19. Expression of CDX2 in normal and neoplastic human colon tissue and during differentiation of an in vitro model system. Qualtrough, D., Hinoi, T., Fearon, E., Paraskeva, C. Gut (2002) [Pubmed]
  20. CDX1 expression is reduced in colorectal carcinoma and is associated with promoter hypermethylation. Pilozzi, E., Onelli, M.R., Ziparo, V., Mercantini, P., Ruco, L. J. Pathol. (2004) [Pubmed]
  21. Cdx1 homeobox gene during human colon cancer progression. Domon-Dell, C., Schneider, A., Moucadel, V., Guerin, E., Guenot, D., Aguillon, S., Duluc, I., Martin, E., Iovanna, J., Launay, J.F., Duclos, B., Chenard, M.P., Meyer, C., Oudet, P., Kedinger, M., Gaub, M.P., Freund, J.N. Oncogene (2003) [Pubmed]
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