Giampazolias, E. et al. (2017) Mitochondrial permeabilization engages NF-κB-dependent anti-tumour activity under caspase deficiency. Nature Cell Biology, 19(9), pp. 1116-1129. (doi: 10.1038/ncb3596) (PMID:28846096) (PMCID:PMC5624512)
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Abstract
Apoptosis represents a key anti-cancer therapeutic effector mechanism. During apoptosis, mitochondrial outer membrane permeabilization (MOMP) typically kills cells even in the absence of caspase activity. Caspase activity can also have a variety of unwanted consequences that include DNA damage. We therefore investigated whether MOMP-induced caspase-independent cell death (CICD) might be a better way to kill cancer cells. We find that cells undergoing CICD display potent pro-inflammatory effects relative to apoptosis. Underlying this, MOMP was found to stimulate NF-κB activity through the downregulation of inhibitor of apoptosis proteins. Strikingly, engagement of CICD displays potent anti-tumorigenic effects, often promoting complete tumour regression in a manner dependent on intact immunity. Our data demonstrate that by activating NF-κB, MOMP can exert additional signalling functions besides triggering cell death. Moreover, they support a rationale for engaging caspase-independent cell death in cell-killing anti-cancer therapies.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Blyth, Professor Karen and Ichim, Dr Gabriel and Cloix, Dr Catherine and Milling, Professor Simon and Roca, Alba and Ryan, Professor Kevin and Machesky, Professor Laura and Giampazolias, Mr Evangelos and Fort, Loic and Woodham, Emma and Tait, Professor Stephen and Lopez, Dr Jonathan and Cao, Dr Kai |
Authors: | Giampazolias, E., Zunino, B., Dhayade, S., Bock, F., Cloix, C., Cao, K., Roca, A., Lopez, J., Ichim, G., Proïcs, E., Rubio-Patiño, C., Fort, L., Yatim, N., Woodham, E., Orozco, S., Taraborrelli, L., Peltzer, N., Lecis, D., Machesky, L., Walczak, H., Albert, M. L., Milling, S., Oberst, A., Ricci, J.-E., Ryan, K. M., Blyth, K., and Tait, S. W.G. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
Journal Name: | Nature Cell Biology |
Publisher: | Nature Publishing Group |
ISSN: | 1465-7392 |
ISSN (Online): | 1476-4679 |
Published Online: | 28 August 2017 |
Copyright Holders: | Copyright © 2017 Macmillan Publishers Limited, part of Springer Nature |
First Published: | First published in Nature Cell Biology 19(9):1116-1129 |
Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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