Requirement of inositol 1,4,5-trisphosphate receptors for tumor-mediated lymphocyte apoptosis

Camia Steinmann, Megan L. Landsverk, José M. Barral, Darren Boehning

    Research output: Contribution to journalArticlepeer-review

    17 Scopus citations

    Abstract

    Tumor cells strategically down-regulate Fas receptor expression to evade immune attack and up-regulate expression of Fas ligand to promote apoptosis of in filtrating T lymphocytes. Many pathways leading to apoptotic cell death require calcium release from inositol 1,4,5-trisphosphate receptors (IP 3Rs). Here, we show that Fas-dependent killing of Jurkat T lymphoma cells by SW620 colon cancer cells requires calcium release from IP3R. General suppression of IP3R signaling significantly reduced SW620-mediated Jurkat cell apoptosis. Significantly, a specific inhibitor of apoptotic calcium release from IP3R strongly blocked lymphocyte apoptosis. Thus, selective pharmacological targeting of apoptotic calcium release from IP3R may enhance tumor cell immunogenicity.

    Original languageEnglish (US)
    Pages (from-to)13506-13509
    Number of pages4
    JournalJournal of Biological Chemistry
    Volume283
    Issue number20
    DOIs
    StatePublished - May 16 2008

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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