Mechanisms of PECAM-1-mediated cytoprotection and implications for cancer cell survival.
Defects in apoptotic pathways can promote cancer development and cause cancers to become resistant to chemotherapy. The cell adhesion and signaling molecule PECAM-1 has been shown to potently suppress apoptosis in a variety of cellular systems. PECAM-1 expression has been reported on a variety of human malignancies-especially hematopoietic and vascular cell cancers-but the significance of this expression has not been fully explored. The ability of PECAM-1 to inhibit apoptosis makes it an attractive candidate as a molecule that may promote cancer development and/or confer resistance to chemotherapeutic treatment. The exact mechanisms by which PECAM-1 mediates its cytoprotection have not been fully defined, but its anti-apoptotic effects have been shown to require both homophilic binding and intracellular signaling via its immunoreceptor tyrosine-based inhibitory motif (ITIM) domains. In this review, we will discuss the data regarding PECAM-1's anti-apoptotic effects and ways in which this cytoprotection may be clinically relevant to the development and/or treatment of hematologic malignancies that express this vascular cell-specific surface molecule.
Bergom
Carmen
C
Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, Milwaukee, WI, USA. CRBergom@bcsew.edu
Gao
Cunji
C
Newman
Peter J
PJ
D000818:Animals; D002470:Cell Survival; D019610:Cytoprotection; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D047908:Intracellular Signaling Peptides and Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases