He GW, Günther C, Thonn V, Yu YQ, Martini E, Buchen B, Neurath M, Stürzl M, Becker C (2017)
Publication Type: Journal article
Publication year: 2017
Book Volume: 214
Pages Range: 1655-1662
Journal Issue: 6
DOI: 10.1084/jem.20160442
Cancer cells often acquire capabilities to evade cell death induced by current chemotherapeutic treatment approaches. Caspase-8, a central initiator of death receptor-mediated apoptosis, for example, is frequently inactivated in human cancers via multiple mechanisms such as mutation. Here, we show an approach to overcome cell death resistance in caspase-8-deficient colorectal cancer (CRC) by induction of necroptosis. In both a hereditary and a xenograft mouse model of caspase-8-deficient CRC, second mitochondria-derived activator of caspase (SMAC) mimetic treatment induced massive cell death and led to regression of tumors. We further demonstrate that receptor-interacting protein kinase 3 (RIP3), which is highly expressed in mouse models of CRC and in a subset of human CRC cell lines, is the deciding factor of cancer cell susceptibility to SMAC mimetic-induced necroptosis. Thus, our data implicate that it may be worthwhile to selectively evaluate the efficacy of SMAC mimetic treatment in CRC patients with caspase-8 deficiency in clinical trials for the development of more effective personalized therapy.
APA:
He, G.-W., Günther, C., Thonn, V., Yu, Y.-Q., Martini, E., Buchen, B.,... Becker, C. (2017). Regression of apoptosis-resistant colorectal tumors by induction of necroptosis in mice. Journal of Experimental Medicine, 214(6), 1655-1662. https://doi.org/10.1084/jem.20160442
MLA:
He, Gui-Wei, et al. "Regression of apoptosis-resistant colorectal tumors by induction of necroptosis in mice." Journal of Experimental Medicine 214.6 (2017): 1655-1662.
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