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Gene Review

DCC  -  DCC netrin 1 receptor

Homo sapiens

Synonyms: CRC18, CRCR1, Colorectal cancer suppressor, IGDCC1, Immunoglobulin superfamily DCC subclass member 1, ...
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Disease relevance of DCC

  • Heterozygous mutations are thought to lead to a loss of function and result in congenital mirror movements. In the heterozygous mouse neuronal axons fail to cross the midline resulting in absence of the corpus callosum and hippocampal commissure [1].
  • DCC (deleted in colorectal cancer) is postulated to function as transmembrane receptor for the axon and cell guidance factor netrin-1 [2].
  • Four of the five tumors with associated adenocarcinoma showed LOH of the DCC gene; in three of these four tumors, the PDNC and adenomatous components showed LOH of the same allele [3].
  • These findings suggest epitope spreading between the Tr antigen and the MAZ-DCC complex and offer a possible model of immune-mediated cerebellar disease [4].
  • Alterations of the p53 and DCC genes occurred frequently both in differentiated and in undifferentiated gastric carcinomas [5].
  • LOH at the DCC locus was a frequent occurrence in carcinomas (58 per cent; 11/19 informative cases) but was infrequent in adenomas (14 per cent; 1/7) [5].

Psychiatry related information on DCC


High impact information on DCC


Chemical compound and disease context of DCC


Biological context of DCC


Anatomical context of DCC


Associations of DCC with chemical compounds

  • Inhibition of Src family kinases reduced DCC tyrosine phosphorylation and blocked both axon attraction and outgrowth of neurons in response to netrin [11].
  • We also find no evidence for an interaction between DCC and heparin and instead demonstrate that a loop on the fifth fibronectin type III repeat of DCC previously implicated in mediating interactions with heparin is important for sNetrin binding [24].
  • Mucosal protein levels of DCC were also reduced in 7 of 10 (70%) placebo-treated patients compared to only 2 of 10 (20%) of patients treated with folate [13].
  • Heparinase and heparitinase treatment of cells reduced binding of DCC-Ig, suggesting that heparan sulfate proteoglycans are cell-surface DCC ligand(s) [14].
  • Here we show that DCC in both commissural neurons and immortalized cells, is partially associated with cholesterol- and sphingolipid-enriched membrane domains named lipid rafts [25].

Physical interactions of DCC

  • Together our results indicate that the growth-promoting function of netrin-1 may require a receptor complex containing DCC and A2b [26].
  • In neuronal cells, MAZ interacts with DCC (Deleted in Colorectal Cancer product), the receptor for netrin-1, a neuronal survival factor [4].
  • A mutant Siah protein lacking the amino-terminal Ubc-binding sequences complexed with DCC, but did not degrade it [2].
  • Removal of the DCC-interacting domain on DIP13 alpha abolishes its ability to enhance DCC-induced apoptosis [27].

Enzymatic interactions of DCC


Regulatory relationships of DCC

  • Specific ubiquitin-proteasome inhibitors prevented the netrin-induced DCC cleavage and decrease of cell surface DCC [32].
  • Taken together, the data imply that the Sina/Siah proteins regulate DCC and perhaps other proteins via the ubiquitin-proteasome pathway [2].
  • Expression of DCC did not modulate constitutive or induced expression of MUC2, nor did DCC induce a mature goblet cell phenotype [33].
  • Inhibition of endogenous DIP13 alpha expression by small interfering RNA blocks DCC-induced apoptosis [27].

Other interactions of DCC

  • Previous studies have failed to show a direct interaction of DCC with netrin-1 (ref. 10), suggesting the possibility of an additional receptor or co-receptor [26].
  • These data demonstrate localization of a gene for FJP to chromosome 18q21.1 by linkage, and they raise the possibility that either DCC or DPC4 could be responsible for FJP [19].
  • This analysis revealed frequent deletions in known tumor suppressor genes (RB1, DCC, NME), a number of previously described sites of candidate tumor suppressor genes (3p, 9p, 9q, 10q, 11p, 11q and 17p), as well as several novel sites (2p, 3q, 5p, 12q, 18p and 20p) [34].
  • Interestingly, only the N-terminal domain (LNT) could bind to DCC and UNC5H1 [35].
  • Immunofluorescence studies suggested the Sina/Siah proteins localized predominantly in the cytoplasm and in association with DCC [2].

Analytical, diagnostic and therapeutic context of DCC



  1. Congenital mirror movements: a clue to understanding bimanual motor control. Galléa, C., Popa, T., Billot, S., Méneret, A., Depienne, C., Roze, E. J. Neurol. (2011) [Pubmed]
  2. Mammalian homologs of seven in absentia regulate DCC via the ubiquitin-proteasome pathway. Hu, G., Zhang, S., Vidal, M., Baer, J.L., Xu, T., Fearon, E.R. Genes Dev. (1997) [Pubmed]
  3. Concordance of genetic alterations in poorly differentiated colorectal neuroendocrine carcinomas and associated adenocarcinomas. Vortmeyer, A.O., Lubensky, I.A., Merino, M.J., Wang, C.Y., Pham, T., Furth, E.E., Zhuang, Z. J. Natl. Cancer Inst. (1997) [Pubmed]
  4. The MAZ protein is an autoantigen of Hodgkin's disease and paraneoplastic cerebellar dysfunction. Bataller, L., Wade, D.F., Graus, F., Rosenfeld, M.R., Dalmau, J. Ann. Neurol. (2003) [Pubmed]
  5. The sequential accumulation of genetic alterations characteristic of the colorectal adenoma-carcinoma sequence does not occur between gastric adenoma and adenocarcinoma. Maesawa, C., Tamura, G., Suzuki, Y., Ogasawara, S., Sakata, K., Kashiwaba, M., Satodate, R. J. Pathol. (1995) [Pubmed]
  6. The DCC protein and colon cancer. Swaim, M.W. N. Engl. J. Med. (1997) [Pubmed]
  7. Deleted in Colorectal Cancer (DCC) encodes a netrin receptor. Keino-Masu, K., Masu, M., Hinck, L., Leonardo, E.D., Chan, S.S., Culotti, J.G., Tessier-Lavigne, M. Cell (1996) [Pubmed]
  8. Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers. Thiagalingam, S., Lengauer, C., Leach, F.S., Schutte, M., Hahn, S.A., Overhauser, J., Willson, J.K., Markowitz, S., Hamilton, S.R., Kern, S.E., Kinzler, K.W., Vogelstein, B. Nat. Genet. (1996) [Pubmed]
  9. The DCC protein and prognosis in colorectal cancer. Shibata, D., Reale, M.A., Lavin, P., Silverman, M., Fearon, E.R., Steele, G., Jessup, J.M., Loda, M., Summerhayes, I.C. N. Engl. J. Med. (1996) [Pubmed]
  10. Scrambled exons. Nigro, J.M., Cho, K.R., Fearon, E.R., Kern, S.E., Ruppert, J.M., Oliner, J.D., Kinzler, K.W., Vogelstein, B. Cell (1991) [Pubmed]
  11. Activation of FAK and Src are receptor-proximal events required for netrin signaling. Li, W., Lee, J., Vikis, H.G., Lee, S.H., Liu, G., Aurandt, J., Shen, T.L., Fearon, E.R., Guan, J.L., Han, M., Rao, Y., Hong, K., Guan, K.L. Nat. Neurosci. (2004) [Pubmed]
  12. Interaction of Myc-associated zinc finger protein with DCC, the product of a tumor-suppressor gene, during the neural differentiation of P19 EC cells. Ugai, H., Li, H.O., Komatsu, M., Tsutsui, H., Song, J., Shiga, T., Fearon, E., Murata, T., Yokoyama, K.K. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  13. Folic acid mediated attenuation of loss of heterozygosity of DCC tumor suppressor gene in the colonic mucosa of patients with colorectal adenomas. Nagothu, K.K., Jaszewski, R., Moragoda, L., Rishi, A.K., Finkenauer, R., Tobi, M., Naumoff, J.A., Dhar, R., Ehrinpreis, M., Kucuk, O., Majumdar, A.P. Cancer Detect. Prev. (2003) [Pubmed]
  14. Deleted in colorectal carcinoma (DCC) binds heparin via its fifth fibronectin type III domain. Bennett, K.L., Bradshaw, J., Youngman, T., Rodgers, J., Greenfield, B., Aruffo, A., Linsley, P.S. J. Biol. Chem. (1997) [Pubmed]
  15. Low expression of reduced folate carrier-1 and folylpolyglutamate synthase correlates with lack of a deleted in colorectal carcinoma mRNA splice variant in normal-appearing mucosa of colorectal carcinoma patients. Wettergren, Y., Odin, E., Nilsson, S., Willen, R., Carlsson, G., Gustavsson, B. Cancer Detect. Prev. (2005) [Pubmed]
  16. Focal adhesion kinase in netrin-1 signaling. Ren, X.R., Ming, G.L., Xie, Y., Hong, Y., Sun, D.M., Zhao, Z.Q., Feng, Z., Wang, Q., Shim, S., Chen, Z.F., Song, H.J., Mei, L., Xiong, W.C. Nat. Neurosci. (2004) [Pubmed]
  17. Phosphatidylinositol transfer protein-alpha in netrin-1-induced PLC signalling and neurite outgrowth. Xie, Y., Ding, Y.Q., Hong, Y., Feng, Z., Navarre, S., Xi, C.X., Zhu, X.J., Wang, C.L., Ackerman, S.L., Kozlowski, D., Mei, L., Xiong, W.C. Nat. Cell Biol. (2005) [Pubmed]
  18. Genetic alterations in sporadic and Crohn's-associated adenocarcinomas of the small intestine. Rashid, A., Hamilton, S.R. Gastroenterology (1997) [Pubmed]
  19. A gene for familial juvenile polyposis maps to chromosome 18q21.1. Howe, J.R., Ringold, J.C., Summers, R.W., Mitros, F.A., Nishimura, D.Y., Stone, E.M. Am. J. Hum. Genet. (1998) [Pubmed]
  20. Turning of retinal growth cones in a netrin-1 gradient mediated by the netrin receptor DCC. de la Torre, J.R., Höpker, V.H., Ming, G.L., Poo, M.M., Tessier-Lavigne, M., Hemmati-Brivanlou, A., Holt, C.E. Neuron (1997) [Pubmed]
  21. Netrin 1 mediates spinal cord oligodendrocyte precursor dispersal. Tsai, H.H., Tessier-Lavigne, M., Miller, R.H. Development (2003) [Pubmed]
  22. DCC regulates cell adhesion in human colon cancer derived HT-29 cells and associates with ezrin. Martín, M., Simon-Assmann, P., Kedinger, M., Martin, M., Mangeat, P., Real, F.X., Fabre, M. Eur. J. Cell Biol. (2006) [Pubmed]
  23. Collision tumour in the pelvic cavity: rectal leiomyosarcoma and prostate adenocarcinoma. Pavelic, J., Lamovec, J., Novak, J., Gall-Troselj, K., Kapitanovic, S., Pavelic, K. J. Cancer Res. Clin. Oncol. (2000) [Pubmed]
  24. Netrin binds discrete subdomains of DCC and UNC5 and mediates interactions between DCC and heparin. Geisbrecht, B.V., Dowd, K.A., Barfield, R.W., Longo, P.A., Leahy, D.J. J. Biol. Chem. (2003) [Pubmed]
  25. DCC association with lipid rafts is required for netrin-1-mediated axon guidance. Hérincs, Z., Corset, V., Cahuzac, N., Furne, C., Castellani, V., Hueber, A.O., Mehlen, P. J. Cell. Sci. (2005) [Pubmed]
  26. Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor. Corset, V., Nguyen-Ba-Charvet, K.T., Forcet, C., Moyse, E., Chédotal, A., Mehlen, P. Nature (2000) [Pubmed]
  27. Mediation of the DCC apoptotic signal by DIP13 alpha. Liu, J., Yao, F., Wu, R., Morgan, M., Thorburn, A., Finley, R.L., Chen, Y.Q. J. Biol. Chem. (2002) [Pubmed]
  28. Quantification of expression of netrins, slits and their receptors in human prostate tumors. Latil, A., Chêne, L., Cochant-Priollet, B., Mangin, P., Fournier, G., Berthon, P., Cussenot, O. Int. J. Cancer (2003) [Pubmed]
  29. Potential role and chronology of abnormal expression of the Deleted in Colon Cancer (DCC) and the p53 proteins in the development of gastric cancer. Graziano, F., Cascinu, S., Staccioli, M.P., Catalano, V., Rossi, M.C., Baldelli, A.M., Giordani, P., Muretto, P., Catalano, G. BMC Cancer (2001) [Pubmed]
  30. p53, DCC and thymidylate synthase as predictors of survival after resection of hepatic metastases from colorectal cancer. Saw, R.P., Koorey, D., Painter, D., Gallagher, P.J., Solomon, M.J. The British journal of surgery. (2002) [Pubmed]
  31. Bcl-2 expression and allelic loss of the p53 gene in gastric carcinomas. Saegusa, M., Takano, Y., Kamata, Y., Okayasu, J. J. Cancer Res. Clin. Oncol. (1996) [Pubmed]
  32. Netrin induces down-regulation of its receptor, Deleted in Colorectal Cancer, through the ubiquitin-proteasome pathway in the embryonic cortical neuron. Kim, T.H., Lee, H.K., Seo, I.A., Bae, H.R., Suh, D.J., Wu, J., Rao, Y., Hwang, K.G., Park, H.T. J. Neurochem. (2005) [Pubmed]
  33. Altered phenotype of HT29 colonic adenocarcinoma cells following expression of the DCC gene. Velcich, A., Corner, G., Palumbo, L., Augenlicht, L. Oncogene (1999) [Pubmed]
  34. Allelic loss and somatic differentiation in human male germ cell tumors. Murty, V.V., Bosl, G.J., Houldsworth, J., Meyers, M., Mukherjee, A.B., Reuter, V., Chaganti, R.S. Oncogene (1994) [Pubmed]
  35. Characterization of the receptors for axon guidance factor netrin-4 and identification of the binding domains. Qin, S., Yu, L., Gao, Y., Zhou, R., Zhang, C. Mol. Cell. Neurosci. (2007) [Pubmed]
  36. Expression of DCC and netrin-1 in normal human endometrium and its implication in endometrial carcinogenesis. Kato, H.D., Kondoh, H., Inoue, T., Asanoma, K., Matsuda, T., Arima, T., Kato, K., Yoshikawa, T., Wake, N. Gynecol. Oncol. (2004) [Pubmed]
  37. Prognostic significance of the deleted in colorectal cancer gene protein expression in high-risk resected gastric carcinoma. Bamias, A.T., Bai, M.C., Agnantis, N.J., Michael, M.C., Alamanos, Y.P., Stefanaki, S.V., Razi, E.D., Skarlos, D.V., Kappas, A.M., Pavlidis, N.A. Cancer Invest. (2003) [Pubmed]
  38. Evaluation of genetic mutations of tumor suppresser genes in colorectal cancer patients. Kubo, H., Miki, C., Kusunoki, M. Hepatogastroenterology (2004) [Pubmed]
  39. Expression and alternative splicing of the deleted in colorectal cancer (DCC) gene in normal and malignant tissues. Reale, M.A., Hu, G., Zafar, A.I., Getzenberg, R.H., Levine, S.M., Fearon, E.R. Cancer Res. (1994) [Pubmed]
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