CEACAM1

The carcinoembryonic antigen-related cell adhesion molecule CEACAM1 has a relative molecular mass ranging between 110,000 to 160,000 (M_r 110K - 160K) due to its multiple and variable N-glycosylations. CEACAM1 is a multifunctional, homophilic adhesion receptor molecule. In addition, its transmembrane signaling leads to a variety of cellular responses including regulation of proliferation, differentiation, tumor growth, angiogenesis, apoptosis and modulation of the innate and adaptive immune response. CEACAM1 mediates cell-cell adhesion by homophilic binding. The N-terminal domains of CEACAM1 are required for these interactions and both the long (CEACAM1-L) and the short (CEACAM1-S) isoforms mediate adhesion. The homophilic binding of CEACAM1 is regulated by its cis-dimerization, phosphorylation status and calmodulin binding. Furthermore, cleavage of the cytoplasmic tail of CEACAM1-L by caspase-3 modifies the adhesive activity. Heterophilic interactions of human CEACAM5 (CEA) and CEACAM6 have also been reported. Due to its frequently decreased expression in epithelial tumors, CEACAM1 was considered to be a tumor suppressor. Various cell culture and orthopic xenograft model studies have provided further evidence for this hypothesis. In human melanoma, CEACAM1 associates in cis with integrin α_vβ₃ and may promote cellular invasion. CEACAM1 is a potent co-regulator of B cell receptor complex (BCR)-induced activation. In granulocytes CEACAM1 is generally accepted to be a positive regulator of effector functions in neutrophils. In addition, CEACAM1 was found to regulate the clearance of insulin by regulating endocytosis of the insulin receptor.