論文 - 詳細
| RRC ID | 82078 |
|---|---|
| 著者 | Yoshizawa K, Matsura A, Shimada M, Ishida-Ishihara S, Sato F, Yamamoto T, Yaguchi K, Kawamoto E, Kuroda T, Matsuo K, Tamaoki N, Sakai R, Shimada Y, Mishra M, Uehara R. |
| タイトル | Tetraploidy-linked sensitization to CENP-E inhibition in human cells. |
| ジャーナル | Mol Oncol |
| Abstract |
Tetraploidy is a hallmark of cancer cells, and tetraploidy-selective cell growth suppression is a potential strategy for targeted cancer therapy. However, how tetraploid cells differ from normal diploids in their sensitivity to anti-proliferative treatments remains largely unknown. In this study, we found that tetraploid cells are significantly more susceptible to inhibitors of a mitotic kinesin (CENP-E) than are diploids. Treatment with a CENP-E inhibitor preferentially diminished the tetraploid cell population in a diploid-tetraploid co-culture at optimum conditions. Live imaging revealed that a tetraploidy-linked increase in unsolvable chromosome misalignment caused substantially longer mitotic delay in tetraploids than in diploids upon moderate CENP-E inhibition. This time gap of mitotic arrest resulted in cohesion fatigue and subsequent cell death, specifically in tetraploids, leading to tetraploidy-selective cell growth suppression. In contrast, the microtubule-stabilizing compound paclitaxel caused tetraploidy-selective suppression through the aggravation of spindle multipolarization. We also found that treatment with a CENP-E inhibitor had superior generality to paclitaxel in its tetraploidy selectivity across a broader spectrum of cell lines. Our results highlight the unique properties of CENP-E inhibitors in tetraploidy-selective suppression and their potential use in the development of tetraploidy-targeting interventions in cancer. |
| 巻・号 | 17(6) |
| ページ | 1148-1166 |
| 公開日 | 2023-6-1 |
| DOI | 10.1002/1878-0261.13379 |
| PMID | 36688680 |
| PMC | PMC10257419 |
| MeSH | Cell Line Chromosomal Proteins, Non-Histone* / antagonists & inhibitors Humans Microtubules Mitosis Neoplasms* Paclitaxel / pharmacology Tetraploidy* |
| IF | 6.574 |
| オルトメトリクス指標 |
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 | 17 |
| 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 | HCT116(RCB2979) |