論文 - 詳細
| RRC ID | 85941 |
|---|---|
| 著者 | Bedia JS, Delgado-Gonzalez A, Huang YW, Gonzalez VD, Funingana IG, Rahil Z, Mike A, Lowber A, Vias M, Ashworth A, Brenton JD, Fantl WJ. |
| タイトル | Coordinated protein modules define DNA damage responses to carboplatin at single-cell resolution in human ovarian carcinoma models. |
| ジャーナル | Cell Rep Med |
| Abstract |
Tubo-ovarian high-grade serous carcinoma (HGSC), the most lethal gynecologic malignancy, initially responds to platinum-based chemotherapy, but due to frequent defects in the DNA damage response (DDR), most tumors develop resistance. The molecular mechanisms underlying clinical platinum resistance remain poorly defined with no biomarkers or targeted therapies to improve outcomes. Here, applying mass cytometry, we quantify phosphorylation and abundance of DDR proteins in carboplatin-treated HGSC cell line models. Despite similar levels of intranuclear platinum, a proxy for carboplatin uptake, cells follow divergent fates, reflecting DDR heterogeneity. Unsupervised analysis reveals a continuum of DDR states, and matrix factorization identifies eight protein modules. The activity of one module, containing canonical DDR proteins, increases in carboplatin-sensitive cells. Resistant cells engage a broader DDR protein module. These findings demonstrate the ability of single-cell proteomics to identify functional DDR states and reveal a DDR sensitivity module as a promising biomarker for clinical stratification and therapeutic decisions in HGSC. |
| 巻・号 | 6(9) |
| ページ | 102295 |
| 公開日 | 2025-9-16 |
| DOI | 10.1016/j.xcrm.2025.102295 |
| PII | S2666-3791(25)00368-4 |
| PMID | 40848720 |
| MeSH | Antineoplastic Agents / pharmacology Carboplatin* / pharmacology Carboplatin* / therapeutic use Cell Line, Tumor DNA Damage* / drug effects DNA Repair / drug effects Drug Resistance, Neoplasm / drug effects Female Humans Ovarian Neoplasms* / drug therapy Ovarian Neoplasms* / genetics Ovarian Neoplasms* / metabolism Ovarian Neoplasms* / pathology Phosphorylation / drug effects Proteomics / methods Single-Cell Analysis* / methods |
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オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 7 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | JHOS-2(RCB1521) |