CEA adhesion molecules: multifunctional proteins with signal-regulatory properties

Abstract

The carcinoembryonic antigen family comprises a large number of complex molecules, several of which possess cell adhesion activities. The primordial adhesion molecules of this family are the cell-cell adhesion molecules (C-CAMs), which have been found to be multifunctional, signal-regulatory proteins. C-CAMs inhibit tumor growth, interact with calmodulin, protein tyrosine kinases and protein tyrosine phosphatases, and are subject to specific dimerization reactions. These new insights indicate that C-CAMs are important regulators of cellular functions.

CEACAM1 impedes thyroid cancer growth but promotes invasiveness: a putative mechanism for early metastases

“…The loss of cell-cell binding that closely correlates with differentiation and the invasive potential of malignant tumors is accompanied by alteration in expression of cell adhesion molecules (Pignatelli and Vessey, 1994). Dysregulated CEACAM1 protein expression in particular has been noted in several forms of solid neoplasia including breast (Obrink, 1997;Riethdorf et al, 1997;Plunkett and Ellis, 2002), colorectal Brummer et al, 1995), prostate Luo et al, 1999), bladder (Kleinerman et al, 1996), endometrial (Bamberger et al, 1998) and hepatocellular carcinomas (Takanishi et al, 1997). More frequently, however, downregulation has been observed compared with adjacent non-malignant surrounding structures.…”

“…We also examined the impact of attenuation of endogenous CEACAM1 expression in MRO cells using stable small CEACAM1 restores thyroid carcinoma cell-matrix adhesion CEACAM1 has been recognized as an intercellular adhesion molecule (Obrink, 1997). However, its binding to extracellular matrix components has not clearly been defined.…”

“…CEACAM1 is an example of a transmembrane protein widely expressed by epithelial and endothelial cells, and most types of hematopoietic cells tissues (Prall et al, 1996;Obrink, 1997;Singer et al, 2000;Plunkett and Ellis, 2002). CEACAM1 shows both homophilic adhesion Ocklind, 1984 1446/id as well as heterophilic binding to other CEA family members in vitro (Oikawa et al, 1992) and is believed to be an important player in maintenance of normal tissue architecture.…”

The CEACAM1-mediated apoptosis pathway is activated by CEA and triggers dual cleavage of CEACAM1

“…The CEACAM1-4L domain contains two tyrosine residues that recruit and activate pp60 c-src (Brummer et al, 1995) or the phosphatases SHP1 and -2 (Huber et al, 1999) upon phosphorylation. Signal transduction through the cytoplasmic domains appears to be important for the tumour suppressor function of CEACAM1 that has been initially suggested by clinical studies (Neumaier et al, 1993b;Nollau et al, 1997b) and subsequently by in vitro experiments and animal studies (Kunath et al, 1995;Obrink, 1997;Singer et al, 2000).…”

Molecular analysis of neisserial Opa protein interactions with the CEA family of receptors: identification of determinants contributing to the differential specificities of binding

“…Whether these closely related proteins can also function as receptors for the neisserial Opa proteins is still unknown. The CEA gene family belongs to the immunoglobulin (Ig) superfamily (Obrink, 1997). Each CEA family member A. Schematic drawing of CEACAM1±CEACAM8 (Beauchemin et al, 1999) illustrating domain structure and membrane anchorage (according to http://www.cea.uni-freiburg.de).…”