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

Eidelman, Frank J.; Fuks, Abraham; DeMarte, Luisa; Taheri, Maryam Akhavan; Stanners, Clifford P.

doi:10.1083/jcb.123.2.467

Cited by 75 publications

(84 citation statements)

References 50 publications

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“…In these circumstances, it has been proposed that CEA is an important component of the intercellular adhesive forces that allows the epithelium to develop into a multilayered array. This would suggest that unregulated levels of CEA in the normal adult colon could be pro-oncogenic and in fact overproduction of CEA blocks the differentiation program of rat myoblast cells (69). We have shown that PPAR␥ ligands induce an increase in CEA-dependent intercellular adhesion.…”

Section: Discussionmentioning

confidence: 77%

Target Genes of Peroxisome Proliferator-activated Receptor γ in Colorectal Cancer Cells

Gupta¹,

Brockman²,

Sarraf³

et al. 2001

Journal of Biological Chemistry

185

123

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Activation of the nuclear hormone peroxisome proliferator-activated receptor ␥ (PPAR␥) inhibits cell growth and promotes differentiation in a broad spectrum of epithelial derived tumor cell lines. Here we utilized microarray technology to identify PPAR␥ gene targets in intestinal epithelial cells. For each gene, the induction or repression was seen with two structurally distinct PPAR␥ agonists, and the change in expression could be blocked by co-treatment with a specific PPAR␥ antagonist. A majority of the genes could be regulated independently by a retinoid X receptor specific agonist. Genes implicated in lipid transport or storage (adipophilin and liver fatty acid-binding protein) were also activated by agonists of PPAR subtypes ␣ and/or ␦. -independent, carcinoembryonic antigendependent homotypic aggregation, suggesting a potential role for PPAR␥ in regulating intercellular adhesion. Collectively, these results will help define the mechanisms by which PPAR␥ regulates intestinal epithelial cell biology.

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Section: Discussionmentioning

confidence: 77%

Target Genes of Peroxisome Proliferator-activated Receptor γ in Colorectal Cancer Cells

Gupta¹,

Brockman²,

Sarraf³

et al. 2001

Journal of Biological Chemistry

185

123

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“…The inhibitory role of CEA in cell differentiation (Eidelman et al, 1993;Screaton et al, 1997;Taheri et al, 2003) has been extensively documented. Structural studies indicated that the CEA-specific GPI-anchor attached to a self-binding external domain was necessary and sufficient for its inhibitory effects on cell differentiation Taheri et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Transfection procedures were carried out as previously described (Eidelman et al, 1993;Screaton et al, 2000). For details see Supplementary Information.…”

Section: Cell Transfection and Infectionmentioning

confidence: 99%

“…It has been demonstrated that essentially all CEA family members, including GPIanchored CEA and CEACAM6, function as homotypic intercellular adhesion molecules in vitro (Benchimol et al, 1989;Oikawa et al, 1989;Stanners and Fuks, 1998). In contrast with the transmembrane member CEACAM1 (Eidelman et al, 1993;Rojas et al, 1996;Ilantzis et al, 2002;Taheri et al, 2003), CEA and CEACAM6 overexpression inhibits cell differentiation and anoikis in vitro (Eidelman et al, 1993;Ordonez et al, 2000;Screaton et al, 2000;Soeth et al, 2001;Taheri et al, 2003;Duxbury et al, 2004) and in vivo (Chan et al, unpublished results). The structural requirements for the inhibitory effects of CEA on differentiation were demonstrated to depend critically on the CEA-specific GPI anchor attached to self-binding extracellular domains Taheri et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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The human carcinoembryonic antigen (CEA) GPI anchor mediates anoikis inhibition by inactivation of the intrinsic death pathway

Camacho-Leal

Stanners

2007

Oncogene

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Human carcinoembryonic antigen (CEA) is a cell surface adhesion molecule member of the Immunoglobulin Superfamily (IgSF). Aberrant upregulation of CEA is a common feature found in a wide variety of human cancers such as colon, breast and lung. Previous in vitro and in vivo results have demonstrated that CEA can have tumorigenic effects including the inhibition of cell differentiation and anoikis, a specific type of apoptosis triggered by the absence of extracellular matrix-cell contacts. In the present work, we investigate the involvement of the caspase cascade in CEAmediated inhibition of anoikis and the structural requirements for this signal. Expression of CEA and/or a chimeric protein consisting of the NCAM extracellular domain attached to the CEA-GPI anchor correlates with an early inactivation of caspase-9 and activation of the PI3-K/Akt survival pathway, and at later times, inactivation of caspase-8. The CEA-mediated caspase inactivation as well as activation of Akt was not observed by expression of a CEA molecule incapable of self-binding (DNCEA). These results suggest that the intrinsic caspase pathway is involved in the inhibitory effects of anoikis by CEA and this signal is dependent on the presence of self-adhesive extracellular domains and a CEA-GPI anchor.

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“…Different functions were implicated for the CEA protein on tumors; mediating intercellular adhesion strengthens the metastatic potential of the tumor cells (24), disrupting tissue structure and inhibition of cell differentiations (16,25). However, until now, no immunological function was attributed to CEA.…”

Section: Discussionmentioning

confidence: 99%

Carcinoembryonic Antigen (CEA) Inhibits NK Killing via Interaction with CEA-Related Cell Adhesion Molecule 1

Stern

Markel

Arnon

et al. 2005

The Journal of Immunology

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The NK killing activity is regulated by activating and inhibitory NK receptors. All of the activating ligands identified so far are either viral or stress-induced proteins. The class I MHC proteins are the ligands for most of the inhibitory NK receptors. However, in the past few years, several receptors have been identified that are able to inhibit NK killing independently of class I MHC recognition. We have previously demonstrated the existence of a novel inhibitory mechanism of NK cell cytotoxicity mediated by the homophilic carcinoembryonic Ag (CEA)-related cell adhesion molecule 1 (CEACAM1) interactions. In this study, we demonstrate that CEACAM1 also interacts heterophilically with the CEA protein. Importantly, we show that these heterophilic interactions of CEA and CEACAM1 inhibit the killing by NK cells. Because CEA is expressed on a wide range of carcinomas and commonly used as tumor marker, these results represent a novel role for the CEA protein enabling the escape of tumor cells from NK-mediated killing. We further characterize, for the first time, the CEACAM1-CEA interactions. Using functional and binding assays, we demonstrate that the N domains of CEACAM1 and CEA are crucial but not sufficient for both the CEACAM1-CEACAM1 homophilic and CEACAM1-CEA heterophilic interactions. Finally, we suggest that the involvement of additional domains beside the N domain in the heterophilic and homophilic interactions is important for regulating the balance between cis and trans interactions.

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

Cited by 75 publications

References 50 publications

Target Genes of Peroxisome Proliferator-activated Receptor γ in Colorectal Cancer Cells

Target Genes of Peroxisome Proliferator-activated Receptor γ in Colorectal Cancer Cells

The human carcinoembryonic antigen (CEA) GPI anchor mediates anoikis inhibition by inactivation of the intrinsic death pathway

Carcinoembryonic Antigen (CEA) Inhibits NK Killing via Interaction with CEA-Related Cell Adhesion Molecule 1

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