{"database":"biostudies-other","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Laura Sanchez-Burgos"],"funding":["Ministerio de Ciencia, Innovación y Universidades (MCIU)","EC | Horizon Europe | Excellent Science | HORIZON EUROPE Marie Sklodowska-Curie Actions (MSCA)","Fundación Científica Asociación Española Contra el Cáncer (AECC)"],"journal":["EMBO Molecular Medicine"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-SCDT-EMM-2022-15855"],"abstract":["FBXW7 is one of the most frequently mutated tumor suppressors, deficiency of which has been associated with resistance to some anticancer therapies. Through bioinformatics and genome-wide CRISPR screens, we here reveal that FBXW7 deficiency leads to multidrug resistance (MDR). Proteomic analyses found an upregulation of mitochondrial factors as a hallmark of FBXW7 deficiency, which has been previously linked to chemotherapy resistance. Despite this increased expression of mitochondrial factors, functional analyses revealed that mitochondria are under stress, and genetic or chemical targeting of mitochondria is preferentially toxic for FBXW7-deficient cells. Mechanistically, the toxicity of therapies targeting mitochondrial translation such as the antibiotic tigecycline relates to activatio"],"repository":["biostudies-other"],"funding_grant_id":["RTI2018-102204-B-I00","LCF/BQ/IN17/11620001","RTI2018-097596-B-I00","PROYE20101FERN"],"pubmed_authors":["Jorge Mota-Pino","Hector Tejero","Laura Sanchez-Burgos","Oleksandra Sirozh","Belen Navarro-Gonzalez","Elena Fueyo-Marcos","Santiago Garcia-Martin","Matilde Murga","Marta, Elena Anton","Oscar Fernandez-Capetillo","Dr. Fátima Al-Shahrour"],"additional_accession":[]},"is_claimable":false,"name":"Activation of the ISR is a vulnerability for multidrug resistant FBXW7-deficient cells","description":"FBXW7 is one of the most frequently mutated tumor suppressors, deficiency of which has been associated with resistance to some anticancer therapies. Through bioinformatics and genome-wide CRISPR screens, we here reveal that FBXW7 deficiency leads to multidrug resistance (MDR). Proteomic analyses found an upregulation of mitochondrial factors as a hallmark of FBXW7 deficiency, which has been previously linked to chemotherapy resistance. Despite this increased expression of mitochondrial factors, functional analyses revealed that mitochondria are under stress, and genetic or chemical targeting of mitochondria is preferentially toxic for FBXW7-deficient cells. Mechanistically, the toxicity of therapies targeting mitochondrial translation such as the antibiotic tigecycline relates to activatio","dates":{"release":"2022-09-14T00:00:00Z","modification":"2022-09-14T20:00:24.658Z","creation":"2022-09-14T20:00:24.658Z"},"accession":"S-SCDT-EMM-2022-15855","cross_references":{"doi":["10.15252/emmm.202215855"]}}