Giampazolias, E;
Zunino, B;
Dhayade, S;
Bock, F;
Cloix, C;
Cao, K;
Roca, A;
... Tait, SWG; + view all
(2017)
Mitochondrial permeabilization engages NF-kappa B-dependent anti-tumour activity under caspase deficiency.
Nature Cell Biology
, 19
(9)
pp. 1116-1129.
10.1038/ncb3596.
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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.
| Type: | Article |
|---|---|
| Title: | Mitochondrial permeabilization engages NF-kappa B-dependent anti-tumour activity under caspase deficiency |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/ncb3596 |
| Publisher version: | http://doi.org/10.1038/ncb3596 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Cell Biology, CELL-DEATH, TNF-ALPHA, INDUCED APOPTOSIS, CANCER, ACTIVATION, INSTABILITY, INHIBITOR, PATHWAY, KINASE, RIPK1 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10047090 |
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