PXD058213
PXD058213 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Synthetic lethal combinations targeting PLK1-CBX8-GPX4 axis with BRAF and EGFR inhibition in BRAF V600E colorectal cancer |
| 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 | iProX |
| AnnounceDate | 2024-11-25 |
| AnnouncementXML | Submission_2025-03-02_18:50:42.628.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Zhan Zhao |
| SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Q Exactive Plus |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2024-11-24 23:05:32 | ID requested | |
| ⏵ 1 | 2025-03-02 18:50:43 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: Immunoprecipitation-Mass Spectrometry |
Contact List
| 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 | |
Full Dataset Link List
| iProX dataset URI |
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