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

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.