Human carcinoembryonic antigen, an intercellular adhesion molecule, blocks fusion and differentiation of rat myoblasts

doi:10.1083/jcb.123.2.467

This Article

	Full Text (PDF, 1409K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Eidelman, F. J.
	Articles by Stanners, C. P.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Eidelman, F. J.
	Articles by Stanners, C. P.


Social Bookmarking

	What's this?

ARTICLES

Human carcinoembryonic antigen, an intercellular adhesion molecule, blocks fusion and differentiation of rat myoblasts

FJ Eidelman, A Fuks, L DeMarte, M Taheri and CP Stanners
McGill Cancer Centre, Biochemistry Department, McGill University, Montreal, Quebec, Canada.

Human carcinoembryonic antigen (CEA), a widely used tumor marker, is a member of a family of cell surface glycoproteins that are overexpressed in many carcinomas. CEA has been shown to function in vitro as a homotypic intercellular adhesion molecule. This correlation of overproduction of an adhesion molecule with neoplastic transformation provoked a test of the effect of CEA on cell differentiation. Using stable CEA transfectants of the rat L6 myoblast cell line as a model system of differentiation, we show that fusion into myotubes and, in fact, the entire molecular program of differentiation, including creatine phosphokinase upregulation, myogenin upregulation, and beta- actin downregulation are completely abrogated by the ectopic expression of CEA. The blocking of the upregulation of myogenin, a transcriptional regulator responsible for the execution of the entire myogenic differentiation program, indicates that CEA expression intercepts the process at a very early stage. The adhesion function of CEA is essential for this effect since an adhesion-defective N domain deletion mutant of CEA was ineffective in blocking fusion and CEA transfectants treated with adhesion-blocking peptides fused normally. Furthermore, CEA transfectants maintain their high division potential, whereas control transfectants lose division potential with differentiation similarly to the parental cell line. Thus the expression of functional CEA on the surface of cells can block terminal differentiation and maintain proliferative potential.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Stern-Ginossar, N., Nedvetzki, S., Markel, G., Gazit, R., Betser-Cohen, G., Achdout, H., Aker, M., Blumberg, R. S., Davis, D. M., Appelmelk, B., Mandelboim, O. (2007). Intercellular Transfer of Carcinoembryonic Antigen from Tumor Cells to NK Cells. J. Immunol. 179: 4424-4434 [Abstract] [Full Text]
Nicholson, T. B., Stanners, C. P. (2007). Identification of a novel functional specificity signal within the GPI anchor signal sequence of carcinoembryonic antigen. JCB 177: 211-218 [Abstract] [Full Text]
Naghibalhossaini, F., Yoder, A. D., Tobi, M., Stanners, C. P. (2007). Evolution of a Tumorigenic Property Conferred by Glycophosphatidyl-Inositol Membrane Anchors of Carcinoembryonic Antigen Gene Family Members during the Primate Radiation. Mol. Biol. Cell 18: 1366-1374 [Abstract] [Full Text]
Nicholson, T. B., Stanners, C. P. (2006). Specific inhibition of GPI-anchored protein function by homing and self-association of specific GPI anchors. JCB 175: 647-659 [Abstract] [Full Text]
Chan, C. H.F., Cook, D., Stanners, C. P. (2006). Increased colon tumor susceptibility in azoxymethane treated CEABAC transgenic mice. Carcinogenesis 27: 1909-1916 [Abstract] [Full Text]
Stern, N., Markel, G., Arnon, T. I., Gruda, R., Wong, H., Gray-Owen, S. D., Mandelboim, O. (2005). Carcinoembryonic Antigen (CEA) Inhibits NK Killing via Interaction with CEA-Related Cell Adhesion Molecule 1. J. Immunol. 174: 6692-6701 [Abstract] [Full Text]
Naghibalhossaini, F., Stanners, C. P. (2004). Minimal mutations are required to effect a radical change in function in CEA family members of the Ig superfamily. J. Cell Sci. 117: 761-769 [Abstract] [Full Text]
Jantscheff, P., Terracciano, L., Lowy, A., Glatz-Krieger, K., Grunert, F., Micheel, B., Brummer, J., Laffer, U., Metzger, U., Herrmann, R., Rochlitz, C. (2003). Expression of CEACAM6 in Resectable Colorectal Cancer: A Factor of Independent Prognostic Significance. JCO 21: 3638-3646 [Abstract] [Full Text]
Taheri, M., Saragovi, H. U., Stanners, C. P. (2003). The Adhesion and Differentiation-inhibitory Activities of the Immunoglobulin Superfamily Member, Carcinoembryonic Antigen, Can Be Independently Blocked. J. Biol. Chem. 278: 14632-14639 [Abstract] [Full Text]
Muenzner, P., Billker, O., Meyer, T. F., Naumann, M. (2002). Nuclear Factor-kappa B Directs Carcinoembryonic Antigen-related Cellular Adhesion Molecule 1 Receptor Expression in Neisseria gonorrhoeae-infected Epithelial Cells. J. Biol. Chem. 277: 7438-7446 [Abstract] [Full Text]
Finkenzeller, D., Fischer, B., McLaughlin, J., Schrewe, H., Ledermann, B., Zimmermann, W. (2000). Trophoblast Cell-Specific Carcinoembryonic Antigen Cell Adhesion Molecule 9 Is Not Required for Placental Development or a Positive Outcome of Allotypic Pregnancies. Mol. Cell. Biol. 20: 7140-7145 [Abstract] [Full Text]
Screaton, R. A., DeMarte, L., Draber, P., Stanners, C. P. (2000). The Specificity for the Differentiation Blocking Activity of Carcinoembryonic Antigen Resides in Its Glycophosphatidyl-Inositol Anchor. JCB 150: 613-626 [Abstract] [Full Text]
Ordoñez, C., Screaton, R. A., Ilantzis, C., Stanners, C. P. (2000). Human Carcinoembryonic Antigen Functions as a General Inhibitor of Anoikis. Cancer Res. 60: 3419-3424 [Abstract] [Full Text]
Yan, Z., Deng, X., Chen, M., Xu, Y., Ahram, M., Sloane, B. F., Friedman, E. (1997). Oncogenic c-Ki-ras but Not Oncogenic c-Ha-ras Up-regulates CEA Expression and Disrupts Basolateral Polarity in Colon Epithelial Cells. J. Biol. Chem. 272: 27902-27907 [Abstract] [Full Text]
Screaton, R. A., Penn, L. Z., Stanners, C. P. (1997). Carcinoembryonic Antigen, a Human Tumor Marker, Cooperates with Myc and Bcl-2 in Cellular Transformation. JCB 137: 939-952 [Abstract] [Full Text]
Hauck, W., Stanners, C. P. (1995). Transcriptional Regulation of the Carcinoembryonic Antigen Gene. J. Biol. Chem. 270: 3602-3610 [Abstract] [Full Text]
Hunter, I, Lindh, M, Obrink, B (1994). Differential regulation of C-CAM isoforms in epithelial cells. J. Cell Sci. 107: 1205-1216 [Abstract]
Muenzner, P., Naumann, M., Meyer, T. F., Gray-Owen, S. D. (2001). Pathogenic Neisseria Trigger Expression of Their Carcinoembryonic Antigen-related Cellular Adhesion Molecule 1 (CEACAM1; Previously CD66a) Receptor on Primary Endothelial Cells by Activating the Immediate Early Response Transcription Factor, Nuclear Factor-kappa B. J. Biol. Chem. 276: 24331-24340 [Abstract] [Full Text]
Gupta, R. A., Brockman, J. A., Sarraf, P., Willson, T. M., DuBois, R. N. (2001). Target Genes of Peroxisome Proliferator-activated Receptor gamma in Colorectal Cancer Cells. J. Biol. Chem. 276: 29681-29687 [Abstract] [Full Text]
Taheri, M., Saragovi, U., Fuks, A., Makkerh, J., Mort, J., Stanners, C. P. (2000). Self Recognition in the Ig Superfamily. IDENTIFICATION OF PRECISE SUBDOMAINS IN CARCINOEMBRYONIC ANTIGEN REQUIRED FOR INTERCELLULAR ADHESION. J. Biol. Chem. 275: 26935-26943 [Abstract] [Full Text]