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PXD058213

PXD058213 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSynthetic lethal combinations targeting PLK1-CBX8-GPX4 axis with BRAF and EGFR inhibition in BRAF V600E colorectal cancer
DescriptionMetastatic BRAFV600E colorectal cancer (CRC) confers poor prognosis and run into a bottleneck in the current treatment strategies. To identify regulatory pathways independent of the MAPK pathway in BRAFV600E CRC, we performed CRISPR-Cas9 screening, and and find targeting glutathione peroxidase 4 (GPX4) remarkably overcome BRAF inhibitor (BRAFi) ± epidermal growth factor receptor (EGFR) inhibitor (EGFRi) resistance in BRAFV600E CRC. Specifically, BRAFi ± EGFRi induced GPX4 upregulated expression and antagonized ferroptosis. Moreover, polo-like kinase 1 (PLK1) substrate activation promoted PLK1 translocation to the nucleus, activating chromobox protein homolog 8 (CBX8) phosphorylation at Ser265, which induce GPX4 expression. Targeting PLK1 promoted BRAFi ± EGFRi inhibition and triggered ferroptosis in vitro, vivo, organoid, and patient-derived xenograft model. Collectively, we demonstrate a novel PLK1–CBX8–GPX4 signaling axis relaying the ferroptosis mechanism of therapeutic resistance operated independent of MAPK signaling and suggest a clinically actionable strategy to overcome BRAFi ± EGFRi resistance in BRAFV600E CRC.
HostingRepositoryiProX
AnnounceDate2024-11-25
AnnouncementXMLSubmission_2025-03-02_18:50:42.628.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterZhan Zhao
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive Plus
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-11-24 23:05:32ID requested
12025-03-02 18:50:43announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Immunoprecipitation-Mass Spectrometry
Contact List
Jinghua Pan
contact affiliationThe First Affiliated Hospital of Jinan University
contact emailhuajanve@foxmail.com
lab head
Zhan Zhao
contact affiliationThe First Affiliated Hospital of Jinan University
contact emailallenzhao1218@163.com
dataset submitter
Full Dataset Link List
iProX dataset URI