{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Fournier LA"],"funding":["Terry Fox Research Institute"],"pagination":["2949"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11394604"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["16(17)"],"pubmed_abstract":["ARID1A is the core DNA-binding subunit of the BAF chromatin remodeling complex and is mutated in about 8% of all cancers. The frequency of ARID1A loss varies between cancer subtypes, with clear cell ovarian carcinoma (CCOC) presenting the highest incidence at > 50% of cases. Despite a growing understanding of the consequences of ARID1A loss in cancer, there remains limited targeted therapeutic options for ARID1A-deficient cancers. Using a genome-wide CRISPR screening approach, we identify KEAP1 as a genetic dependency of ARID1A in CCOC. Depletion or chemical perturbation of KEAP1 results in selective growth inhibition of ARID1A-KO cell lines and edited primary endometrial epithelial cells. While we confirm that KEAP1-NRF2 signalling is dysregulated in ARID1A-KO cells, we suggest that this "],"journal":["Cancers"],"pubmed_title":["Genome-Wide CRISPR Screen Identifies KEAP1 Perturbation as a Vulnerability of ARID1A-Deficient Cells."],"pmcid":["PMC11394604"],"funding_grant_id":["1082"],"pubmed_authors":["Su E","Huntsman DG","White J","Fournier LA","Wells JP","Moksa MM","Lee JS","Trigo-Gonzalez G","Smith T","Hirst M","Wang SL","Shanks A","Wang Y","Stirling PC","Kalantari F"],"additional_accession":[]},"is_claimable":false,"name":"Genome-Wide CRISPR Screen Identifies KEAP1 Perturbation as a Vulnerability of ARID1A-Deficient Cells.","description":"ARID1A is the core DNA-binding subunit of the BAF chromatin remodeling complex and is mutated in about 8% of all cancers. The frequency of ARID1A loss varies between cancer subtypes, with clear cell ovarian carcinoma (CCOC) presenting the highest incidence at > 50% of cases. Despite a growing understanding of the consequences of ARID1A loss in cancer, there remains limited targeted therapeutic options for ARID1A-deficient cancers. Using a genome-wide CRISPR screening approach, we identify KEAP1 as a genetic dependency of ARID1A in CCOC. Depletion or chemical perturbation of KEAP1 results in selective growth inhibition of ARID1A-KO cell lines and edited primary endometrial epithelial cells. While we confirm that KEAP1-NRF2 signalling is dysregulated in ARID1A-KO cells, we suggest that this ","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Aug","modification":"2025-04-04T09:49:13.869Z","creation":"2025-04-04T09:49:13.869Z"},"accession":"S-EPMC11394604","cross_references":{"pubmed":["39272807"],"doi":["10.3390/cancers16172949"]}}