The human carcinoembryonic antigen (CEA) GPI anchor mediates anoikis inhibition by inactivation of the intrinsic death pathway
| Autor: | P Camacho-Leal, C P Stanners |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Cancer Research
endocrine system diseases Glycosylphosphatidylinositols MAP Kinase Signaling System Cellular differentiation Recombinant Fusion Proteins Blotting Western Apoptosis Myoblasts Phosphatidylinositol 3-Kinases Carcinoembryonic antigen Genetics Extracellular In Situ Nick-End Labeling Animals Anoikis neoplasms Molecular Biology Protein kinase B Neural Cell Adhesion Molecules Caspase Cells Cultured biology Cytochromes c Molecular biology Caspase Inhibitors digestive system diseases Caspase 9 Cell biology Carcinoembryonic Antigen Rats Enzyme Activation biology.protein Immunoglobulin superfamily Neural cell adhesion molecule Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Oncogene. 27(11) |
| ISSN: | 1476-5594 |
| Popis: | 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 CEA-mediated 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 (DeltaNCEA). 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. |
| Databáze: | OpenAIRE |
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