Mechanisms of PECAM-1-mediated cytoprotection and implications for cancer cell survival

Carmen Bergom, Cunji Gao, Peter J. Newman

Research output: Contribution to journalReview articlepeer-review

31 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1409-1421
Number of pages13
JournalLeukemia and Lymphoma
Volume46
Issue number10
DOIs
StatePublished - Oct 2005

Keywords

  • Apoptosis
  • Cancer
  • Leukemia
  • PECAM-1
  • SHP-2

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