論文 - 詳細
| RRC ID | 10847 |
|---|---|
| 著者 | Chu TLH, Connell M, Zhou L, He Z, Won J, Chen H, Rahavi SMR, Mohan P, Nemirovsky O, Fotovati A, Pujana MA, Reid GSD, Nielsen TO, Pante N, Maxwell CA. |
| タイトル | Cell Cycle-Dependent Tumor Engraftment and Migration Are Enabled by Aurora-A. |
| ジャーナル | Mol Cancer Res |
| Abstract |
Cell-cycle progression and the acquisition of a migratory phenotype are hallmarks of human carcinoma cells that are perceived as independent processes but may be interconnected by molecular pathways that control microtubule nucleation at centrosomes. Here, cell-cycle progression dramatically impacts the engraftment kinetics of 4T1-luciferase2 breast cancer cells in immunocompetent BALB/c or immunocompromised NOD-SCID gamma (NSG) mice. Multiparameter imaging of wound closure assays was used to track cell-cycle progression, cell migration, and associated phenotypes in epithelial cells or carcinoma cells expressing a fluorescence ubiquitin cell-cycle indicator. Cell migration occurred with an elevated velocity and directionality during the S-G2-phase of the cell cycle, and cells in this phase possess front-polarized centrosomes with augmented microtubule nucleation capacity. Inhibition of Aurora kinase-A (AURKA/Aurora-A) dampens these phenotypes without altering cell-cycle progression. During G2-phase, the level of phosphorylated Aurora-A at centrosomes is reduced in hyaluronan-mediated motility receptor (HMMR)-silenced cells as is the nuclear transport of TPX2, an Aurora-A-activating protein. TPX2 nuclear transport depends upon HMMR-T703, which releases TPX2 from a complex with importin-α (KPNA2) at the nuclear envelope. Finally, the abundance of phosphorylated HMMR-T703, a substrate for Aurora-A, predicts breast cancer-specific survival and relapse-free survival in patients with estrogen receptor (ER)-negative (n = 941), triple-negative (TNBC) phenotype (n = 538), or basal-like subtype (n = 293) breast cancers, but not in those patients with ER-positive breast cancer (n = 2,218). Together, these data demonstrate an Aurora-A/TPX2/HMMR molecular axis that intersects cell-cycle progression and cell migration.Implications: Tumor cell engraftment, migration, and cell-cycle progression share common regulation of the microtubule cytoskeleton through the Aurora-A/TPX2/HMMR axis, which has the potential to influence the survival of patients with ER-negative breast tumors. Mol Cancer Res; 16(1); 16-31. ©2017 AACR. |
| 巻・号 | 16(1) |
| ページ | 16-31 |
| 公開日 | 2018-1-1 |
| DOI | 10.1158/1541-7786.MCR-17-0417 |
| PII | 1541-7786.MCR-17-0417 |
| PMID | 28993511 |
| MeSH | Animals Aurora Kinase A / genetics* Aurora Kinase A / metabolism Cell Cycle Proteins / metabolism* Female Humans Mice Transfection |
| 引用数 | 10 |
| WOS 分野 | GENETICS & HEREDITY |
| 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 | 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 | NMuMG/Fucci HeLa-FUCCI |