Small Molecule Disruption of RARα/NCoR1 Interaction Inhibits Chaperone-Mediated Autophagy in Cancer

ABSTRACT: Chaperone-mediated autophagy (CMA), a type of selective degradation of cytosolic proteins in lysosomes, is commonly upregulated in cancer cells, contributing to their survival and growth. The lack of a specific target for CMA inhibition has limited CMA blockage to genetic manipulations or global lysosomal function inhibition. Here, using genetic modulation, transcriptional analysis, and functional studies, we demonstrate a regulatory role for the interaction of the retinoic acid receptor alpha (RARα) and its corepressor, the nuclear receptor corepressor 1 (NCoR1), on CMA in non-small cell lung cancer (NSCLC). By targeting the disruption of the NCoR1/RARα complex with a structure-based screening strategy, we identified compound CIM7, a potent and selective CMA inhibitor that has no effect o

SUBMITTER: Mericka McCabe 

PROVIDER: S-SCDT-10_1038-S44321-025-00254-Y | biostudies-other |

REPOSITORIES: biostudies-other