Alternative titles; symbols
HGNC Approved Gene Symbol: CEACAM6
Cytogenetic location: 19q13.2 Genomic coordinates (GRCh38): 19:41,755,530-41,772,211 (from NCBI)
Carcinoembryonic antigen (CEA; 114890) is one of the most widely used tumor markers in serum immunoassay determinations of carcinoma. An apparent lack of absolute cancer specificity for CEA probably results in part from the presence in normal and neoplastic tissues of antigens that share antigenic determinants with the 180-kD form of CEA (Barnett et al., 1988). For background information on the CEA family of genes, see CEACAM1 (109770).
Barnett et al. (1988) presented sequences of a 'normal crossreacting antigen' (NCA) and showed that CEA and NCA, although closely related in sequence, are structurally and probably functionally distinct.
Using immunohistochemical analysis, Scholzel et al. (2000) showed that human CEACAM6 was expressed in granulocytes and epithelial cells in various organs. In squamous epithelial cells, CEACAM6 displayed nonpolarized cell surface localization and cytoplasmic localization, but in simple epithelia, CEACAM6 was present on the apical surface. CEACAM6 exhibited apical expression throughout colon development and was found in the upper half of developing crypts. CEACAM6 expression correlated with expression of CD95 (FAS; 134637) and with apoptosis at the table region of normal colon, but CEACAM6 was absent from highly proliferating cells at the base of colonic crypts.
By in situ hybridization, Willcocks et al. (1989) mapped NCA to 19q13 in the same region as CEA. The localization was supported by studies with a somatic cell hybrid cell line. By a combination of Southern blot analysis and in situ hybridization, Inazawa et al. (1989) localized the gene to 19q13.2.
In 15 patients with Crohn disease (CD; see 266600) and 9 controls, Barnich et al. (2007) found that adherent-invasive E. coli (AIEC) adhesion was dependent on type 1 pili expression on the bacterial surface and on CEACAM6 expression on the apical surface of ileal epithelial cells. CEACAM6 acted as a receptor for AIEC adhesion and was upregulated in the ileal mucosa of CD patients compared to colonic mucosa or to controls. In vitro studies showed increased CEACAM6 expression in cultured intestinal epithelial cells after IFN-gamma (147570) or TNF-alpha (191160) stimulation and after infection with AIEC.
By desensitizing neutrophils to stimulation by various combinations of anti-CD66 antibodies, Skubitz and Skubitz (2008) showed that the 4 neutrophil CEACAMs, including CEACAM6, had significant independent signaling functions. However, the results suggested that the CEACAMs may also act in combination, with CEACAM1 having a unique role.
By screening a panel of pancreatic cancer cell lines for sensitivity to adenovirus, followed by differential gene expression analysis between sensitive and insensitive cells, Wang et al. (2009) found that CEACAM6 expression correlated with the sensitivity of tumor cells to the virus. CEACAM6 blocked adenovirus trafficking to the nucleus through the SRC (190090) pathway, interfering with cancer cell cytoskeleton and reducing adenoviral infection. Knockdown of CEACAM6 with small interfering RNA significantly increased adenovirus replication and antitumor efficacy of oncolytic adenovirus in a mouse xenograft tumor model. Wang et al. (2009) concluded that CEACAM6 is a tumor-associated gene that affects the ability of cancer cells to be infected with adenovirus.
Mouse neutrophils do not bind the human-restricted pathogen Neisseria gonorrhoeae. Sarantis and Gray-Owen (2012) showed that introducing any of the gonorrheal Opa-binding human neutrophil CEACAMs into a murine neutrophil cell line allowed binding and entry of Neisseria. CEACAM1 and CEACAM6 both bound and allowed entry of the bacterium, but they mediated little neutrophil activation. In contrast, uptake via CEACAM3 (609142) induced an oxidative burst and intracellular granule release comparable to that seen during human neutrophil infection. Coexpression of CEACAM3 with either CEACAM1 or CEACAM6 potentiated CEACAM3-dependent responses. Sarantis and Gray-Owen (2012) concluded that, although CEACAMs have different functions in neutrophils, they cooperate during gonorrheal infection. Their findings implicated CEACAM3 in the neutrophil innate response to neisserial infection.
Beauchemin et al. (1999) provided a revised nomenclature for the CEA gene family. Based on this nomenclature, the CEA family is composed of the PSG subfamily (see 176390); the CEACAM subfamily, which includes CEACAM1 (BGP), CEACAM3 (CGM1; 609142), CEACAM4 (619159), CEACAM5 (CEA), CEACAM6 (NCA), CEACAM7 (619160), and CEACAM8 (615747); and the CEACAM pseudogene (CEACAMP) subfamily, CEACAMP1 through CEACAMP11, which had originally been named CGM8 through CGM18 (see 109770). The NCA gene was renamed CEACAM6.
Barnett, T., Goebel, S. J., Nothdurft, M. A., Elting, J. J. Carcinoembryonic antigen family: characterization of cDNAs coding for NCA and CEA and suggestion of nonrandom sequence variation in their conserved loop-domains. Genomics 3: 59-66, 1988. [PubMed: 3220478] [Full Text: https://doi.org/10.1016/0888-7543(88)90160-7]
Barnich, N., Carvalho, F. A., Glasser, A.-L., Darcha, C., Jantscheff, P., Allez, M., Peeters, H., Bommelaer, G., Desreumaux, P., Colombel, J.-F., Darfeuille-Michaud, A. CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease. J. Clin. Invest. 117: 1566-1574, 2007. [PubMed: 17525800] [Full Text: https://doi.org/10.1172/JCI30504]
Beauchemin, N., Draber, P., Dveksler, G., Gold, P., Gray-Owen, S., Grunert, F., Hammarstrom, S., Holmes, K. V., Karlsson, A., Kuroki, M., Lin, S.-H., Lucka, L., and 13 others. Redefined nomenclature for members of the carcinoembryonic antigen family. Exp. Cell Res. 252: 243-249, 1999. [PubMed: 11501563] [Full Text: https://doi.org/10.1006/excr.1999.4610]
Inazawa, J., Abe, T., Inoue, K., Misawa, S., Oikawa, S., Nakazato, H., Yoshida, M. C. Regional assignment of nonspecific cross-reacting antigen (NCA) of the CEA gene family to chromosome 19 at band q13.2. Cytogenet. Cell Genet. 52: 28-31, 1989. [PubMed: 2612212] [Full Text: https://doi.org/10.1159/000132833]
Sarantis, H., Gray-Owen, S. D. Defining the roles of human carcinoembryonic antigen-related cellular adhesion molecules during neutrophil responses to Neisseria gonorrhoeae. Infect. Immun. 80: 345-358, 2012. [PubMed: 22064717] [Full Text: https://doi.org/10.1128/IAI.05702-11]
Scholzel, S., Zimmermann, W., Schwarzkopf, G., Grunert, F., Rogaczewski, B., Thompson, J. Carcinoembryonic antigen family members CEACAM6 and CEACAM7 are differentially expressed in normal tissues and oppositely deregulated in hyperplastic colorectal polyps and early adenomas. Am. J. Path. 156: 595-605, 2000. [PubMed: 10666389] [Full Text: https://doi.org/10.1016/S0002-9440(10)64764-5]
Skubitz, K. M., Skubitz, A. P. N. Interdependency of CEACAM-1, -3, -6, and -8 induced human neutrophil adhesion to endothelial cells. J. Transl. Med. 6: 78, 2008. Note: Electronic Article. [PubMed: 19077207] [Full Text: https://doi.org/10.1186/1479-5876-6-78]
Wang, Y., Gangeswaran, R., Zhao, X., Wang, P., Tysome, J., Bhakta, V., Yuan, M., Chikkanna-Gowda, C. P., Jiang, G., Gao, D., Cao, F., Francis, J., Yu, J., Liu, K., Yang, H., Zhang, Y., Zang, W., Chelala, C., Dong, Z., Lemoine, N. CEACAM6 attenuates adenovirus infection by antagonizing viral trafficking in cancer cells. J. Clin. Invest. 119: 1604-1615, 2009. [PubMed: 19411761] [Full Text: https://doi.org/10.1172/JCI37905]
Willcocks, T. C., Craig, S. P., Craig, I. W. Assignment of the coding sequence for carcinoembryonic antigen (CEA) and normal cross-reacting antigen (NCA) to human chromosome 19q13. Ann. Hum. Genet. 53: 141-148, 1989. [PubMed: 2596823] [Full Text: https://doi.org/10.1111/j.1469-1809.1989.tb01778.x]