TBK1 Kinase Addiction in Lung Cancer Cells Is Mediated via Autophagy of Tax1bp1/Ndp52 and Non-Canonical NF-kappa B Signalling

Alice C. Newman, Caroline L. Scholefield, Alain J. Kemp, Michelle Newman, Edward G. McIver, Ahmad Kamal, Simon Wilkinson

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Article numberARTN e50672
Pages (from-to)e50672
Number of pages12
JournalPLoS ONE
Volume7
Issue number11
DOIs
Publication statusPublished - 29 Nov 2012

Keywords

  • ACTIVATION
  • RESTRICTS
  • PROTEIN
  • SURVIVAL
  • PHOSPHORYLATION
  • PROLIFERATION
  • MATURATION
  • REQUIREMENT
  • TANK
  • TUMORIGENESIS

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