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TBK1 kinase addiction in lung cancer cells is mediated via autophagy of Tax1bp1/Ndp52 and non-canonical NF-?B signalling.


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-?B signalling. We propose that this TBK1-dependent mechanism for NF-?B signalling contributes to autophagy addiction in K-Ras driven NSCLC.

SUBMITTER: Newman AC 

PROVIDER: S-EPMC3510188 | BioStudies | 2012-01-01

REPOSITORIES: biostudies

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