PXD058218

PXD058218 is an original dataset announced via ProteomeXchange.

Title	Proteomic and phosphoproteomic analyses for HT-29
Description	Metastatic 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.
HostingRepository	PRIDE
AnnounceDate	2025-02-28
AnnouncementXML	Submission_2025-02-28_11:50:05.280.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	zhan zhao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-11-25 01:36:48	ID requested
⏵ 1	2025-02-28 11:50:05	announced

Dataset with its publication pending

submitter keyword: CBX8, phosphoproteomic, Proteomic, PLK1

Jinghua Pan
contact affiliation	The First Affiliated Hospital of Jinan University
contact email	huajanve@foxmail.com
lab head
zhan zhao
contact affiliation	The First Affiliated Hospital of Jinan University
contact email	allenzhao1218@163.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/2025/02/PXD058218

PRIDE project URI

• PRIDE
  1. PXD058218
     1. Label: PRIDE project
     2. Name: Proteomic and phosphoproteomic analyses for HT-29