Centrosome Amplification in Cancer Disrupts Autophagy and Sensitizes to Autophagy Inhibition.

ABSTRACT: Centrosome amplification (CA), or a numerical increase in centrosomes, is common in human cancers, particularly those with high-risk features. We have discovered that cells with CA have an increased burden of autophagy, a catabolic process whereby autophagosomes engulf damaged organelles and proteins and deliver these contents to the lysosome for degradation and subsequent recycling. Cells with CA demonstrate an accumulation of autophagosomes. We evaluated the alternative hypotheses that CA alters autophagy by modulating microtubule networks and impairing trafficking versus altering lysosome clustering and organization versus chromosome missegregation-induced proteotoxic stress. Using LC3 reporter assays and autophagosome tracking experiments, we demonstrate that CA causes an accumulation

SUBMITTER: Denu RA 

PROVIDER: S-EPMC6942210 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature