PXD029981

PXD029981 is an original dataset announced via ProteomeXchange.

Title	Targeting mitochondrial translation overcomes multidrug resistance in FBXW7-deficient cells
Description	FBXW7 is one of the most frequently mutated tumor suppressors, the deficiency of which has been associated with resistance to some anticancer therapies. Through bioinformatic analyses and genome-wide CRISPR screens, we here reveal that FBXW7 deficiency leads to multi-drug resistance (MDR), to a bigger extent than well-established MDR-drivers such as ABCB1. Proteomic data from FBXW7-deficient cells and human cancer samples identify the upregulation of mitochondrial function as a hallmark of FBXW7 deficiency, which has been previously linked to an increased resistance to chemotherapy. Accordingly, genetic or chemical targeting of mitochondria is preferentially toxic for FBXW7-deficient cells. For instance, targeting mitochondrial translation with the antibiotic Tigecycline efficiently kills FBXW7-deficient cells in vitro and in vivo, by a mechanism that involves activation of the Integrated Stress Response (ISR). Searching for additional drugs that overcome MDR in FBXW7-deficient cells, we found several targeted therapies such as Erlotinib, Dasatinib or Vemurafenib which unexpectedly also activate the ISR. Together, our study reveals that one of the most frequent mutations in cancer reduces the sensitivity to the vast majority of available therapies, and identifies a general principle to overcome such resistance.
HostingRepository	PRIDE
AnnounceDate	2022-06-08
AnnouncementXML	Submission_2022-06-08_07:26:13.272.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eduardo Zarzuela
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-26 08:24:05	ID requested
⏵ 1	2022-06-08 07:26:13	announced

Dataset with its publication pending

submitter keyword: mESCs, TMT, Q Exactive

Javier Muñoz
contact affiliation	Proteomics Unit, Biotechnology Programme, CNIO (Centro Nacional de Investigaciones Oncológicas),Madrid, Spain
contact email	javier.munozperalta@osakidetza.eus
lab head
Eduardo Zarzuela
contact affiliation	Centro Nacional de Investigaciones Oncológicas
contact email	eduzarfer@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/06/PXD029981

PRIDE project URI

• PRIDE
  1. PXD029981
     1. Label: PRIDE project
     2. Name: Targeting mitochondrial translation overcomes multidrug resistance in FBXW7-deficient cells