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.
Mesh Terms:
Autophagy, Carcinoma, Non-Small-Cell Lung, Cell Line, Fluorescent Antibody Technique, Humans, Immunoblotting, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Lentivirus, Lung Neoplasms, NF-kappa B, Neoplasm Proteins, Nuclear Proteins, Protein-Serine-Threonine Kinases, RNA, Small Interfering, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Transcription Factor RelA, Transcription Factor RelB
Autophagy, Carcinoma, Non-Small-Cell Lung, Cell Line, Fluorescent Antibody Technique, Humans, Immunoblotting, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Lentivirus, Lung Neoplasms, NF-kappa B, Neoplasm Proteins, Nuclear Proteins, Protein-Serine-Threonine Kinases, RNA, Small Interfering, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Transcription Factor RelA, Transcription Factor RelB
PLoS ONE
Date: Dec. 05, 2012
PubMed ID: 23209807
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