TBK1 Kinase Addiction in Lung Cancer Cells Is Mediated via Autophagy of Tax1bp1/Ndp52 and Non-Canonical NF-κB Signalling |
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| Authors: | Alice C Newman Caroline L Scholefield Alain J Kemp Michelle Newman Edward G McIver Ahmad Kamal Simon Wilkinson |
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| Institution: | 1. Edinburgh Cancer Research UK Centre, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.; 2. Centre for Therapeutics Discovery, MRC Technology, London, United Kingdom.; Johns Hopkins School of Medicine, United States of America, |
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| Abstract: | K-Ras dependent non-small cell lung cancer (NSCLC) cells are ‘addicted’ to basal autophagy that reprograms cellular metabolism in a lysosomal-sensitive manner. Here we demonstrate that the xenophagy-associated kinase TBK1 drives basal autophagy, consistent with its known requirement in K-Ras-dependent NSCLC proliferation. Furthermore, basal autophagy in this context is characterised by sequestration of the xenophagy cargo receptor Ndp52 and its paralogue Tax1bp1, which we demonstrate here to be a bona fide cargo receptor. Autophagy of these cargo receptors promotes non-canonical NF-κB signalling. We propose that this TBK1-dependent mechanism for NF-κB signalling contributes to autophagy addiction in K-Ras driven NSCLC. |
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