| Title: | Tetraploidy-linked sensitization to CENP-E inhibition in human cells |
| Authors: | Yoshizawa, Koya Browse this author |
| Matsura, Akira Browse this author |
| Shimada, Masaya Browse this author |
| Ishida-Ishihara, Sumire Browse this author |
| Sato, Fuyu Browse this author |
| Yamamoto, Takahiro Browse this author |
| Yaguchi, Kan Browse this author |
| Kawamoto, Eiji Browse this author →KAKEN DB |
| Kuroda, Taruho Browse this author |
| Matsuo, Kazuya Browse this author →KAKEN DB |
| Tamaoki, Nobuyuki Browse this author →KAKEN DB |
| Sakai, Ryuichi Browse this author →KAKEN DB |
| Shimada, Yasuhito Browse this author →KAKEN DB |
| Mishra, Mithilesh Browse this author |
| Uehara, Ryota Browse this author →KAKEN DB |
| Keywords: | chromosome |
| mitosis |
| motor protein |
| ploidy |
| Issue Date: | 24-May-2023 |
| Publisher: | John Wiley & Sons |
| Journal Title: | Molecular oncology |
| Publisher DOI: | 10.1002/1878-0261.13379 |
| 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. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/89323 |
| Appears in Collections: | 生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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