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-kappa B signalling. We propose that this TBK1-dependent mechanism for NF-kappa B signalling contributes to autophagy addiction in K-Ras driven NSCLC. Citation: Newman AC, Scholefield CL, Kemp AJ, Newman M, McIver EG, et al. (2012) TBK1 Kinase Addiction in Lung Cancer Cells Is Mediated via Autophagy of Tax1bp1/Ndp52 and Non-Canonical NF-kappa B Signalling. PLoS ONE 7(11): e50672. doi: 10.1371/journal.pone.0050672
Original language | English |
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Article number | ARTN e50672 |
Pages (from-to) | e50672 |
Number of pages | 12 |
Journal | PLoS ONE |
Volume | 7 |
Issue number | 11 |
DOIs | |
Publication status | Published - 29 Nov 2012 |
Keywords / Materials (for Non-textual outputs)
- ACTIVATION
- RESTRICTS
- PROTEIN
- SURVIVAL
- PHOSPHORYLATION
- PROLIFERATION
- MATURATION
- REQUIREMENT
- TANK
- TUMORIGENESIS