Metabolic resistance to the inhibition of mitochondrial transcription revealed by CRISPR-Cas9 screen

ABSTRACT: Cancer cells depend on mitochondria to sustain their increased metabolic need and mitochondria therefore constitute possible targets for cancer treatment. We recently developed small-molecule inhibitors of mitochondrial transcription (IMTs) that selectively impair mitochondrial gene expression. IMTs have potent antitumor properties in vitro and in vivo, without affecting normal tissues. Because therapy-induced resistance is a major constraint to successful cancer therapy, we investigated mechanisms conferring resistance to IMTs. We employed a CRISPR-Cas9 whole genome screen to determine pathways conferring resistance to acute IMT1 treatment. Loss of genes belonging to VHL and mTORC1 pathways caused resistance to acute IMT1 treatment and the relevance of these pathways was confirmed by chem

SUBMITTER: Dr. Mara Mennuni 

PROVIDER: S-SCDT-EMBOR-2021-53054V1 | biostudies-other |

REPOSITORIES: biostudies-other