bstract
Detachment of adherent epithelial cells from the extracellular matrix induces apoptosis, a process known as anoikis. We have shown that DAP3 is critical for anoikis induction. However, the mechanism for anoikis induction mediated by DAP3 is still unclear. Here, we show that interferon-β promoter stimulator 1 (IPS-1) binds DAP3 and induces anoikis by caspase activation. Recently, IPS-1 has been shown to be critical for antiviral immune responses, although there has been no report of its function in apoptosis induction. We show that overexpression of IPS-1 induces apoptosis by activation of caspase-3, -8, and -9. In addition, IPS-1 knockout mouse embryonic fibroblasts were shown to be resistant to anoikis. Interestingly, IPS-1 expression, recruitment of caspase-8 to IPS-1, and caspase-8 activation were induced after cell detachment. Furthermore, DAP3-mediated anoikis induction was inhibited by knockdown of IPS-1 expression. Therefore, we elucidated a novel function of IPS-1 for anoikis induction by caspase-8 activation.
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Main
Anoikis is a specialized form of apoptosis triggered by loss of cell-matrix attachment, critical for preventing metastasis. This 2009 study examined the role of IPS-1 and DAP3 proteins in mediating anoikis.
IPS-1 was identified as crucial for DAP3-mediated anoikis through caspase-8 activation. This signaling cascade promotes apoptosis in epithelial cells detached from their matrix, providing a natural barrier to cancer metastasis. Understanding this pathway identifies potential targets for enhancing anoikis in cancer cells.
Anoikis and apoptotic pathways in cancer cells are relevant to immune-mediated tumor clearance. NK cells activated by beta glucan can trigger similar apoptotic cascades in tumor cells, potentially complementing intrinsic anoikis mechanisms to limit metastasis.
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Li H., Fujikura D., Harada T., Uehara J., Ikeda H., Goto T., Nishida K., Iwai A., Chida K., Uede T.. IPS-1 is crucial for DAP3-mediated anoikis induction by caspase-8 activation. Cell Death & Differentiation. 2009. DOI: 10.1038/cdd.2009.97.
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