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_2025-08-20_19:09:44.664.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 | |
| ⏵ 2 | 2025-08-20 19:09:45 | announced | 2025-08-21: Add info. |
Publication List
| Zhao Z, He J, Qiu S, Wang L, Huangfu S, Hu Y, Wu Q, Yang Y, Li X, Huang M, Liu S, Guan H, Chen Z, Zhang X, Zhang Y, Ding H, Zhao X, Xiao G, Pan Y, Liu T, Wu Y, Pan J, Targeting PLK1-CBX8-GPX4 axis overcomes BRAF/EGFR inhibitor resistance in BRAFV600E colorectal cancer via ferroptosis. Nat Commun, 16(1):3605(2025) [pubmed] |
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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