Chromosomally unstable tumor cells specifically require KIF18A for proliferation
| العنوان: | Chromosomally unstable tumor cells specifically require KIF18A for proliferation |
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| المؤلفون: | Joseph E. Clayton, Lisa Wood, Carolyn Marquis, Heidi L.H. Malaby, Katelyn A. Queen, Sarah E. Vandal, Cindy L. Fonseca, Jason Stumpff |
| المصدر: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-14 (2021) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Programmed cell death, Cell cycle checkpoint, Paclitaxel, Science, General Physics and Astronomy, Kinesins, Mitosis, macromolecular substances, Spindle Apparatus, Biology, Microtubules, Models, Biological, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Targeted therapies, Microtubule, Chromosome instability, Cell Line, Tumor, Chromosomal Instability, Neoplasms, Humans, Cell Proliferation, Centrosome, Multidisciplinary, Cell Death, Nocodazole, General Chemistry, Cell Cycle Checkpoints, Kinesin, female genital diseases and pregnancy complications, Spindle apparatus, Cell biology, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, Multipolar spindles |
| الوصف: | Chromosomal instability (CIN) is a hallmark of tumor cells caused by changes in the dynamics and control of microtubules that compromise the mitotic spindle. Thus, CIN cells may respond differently than diploid cells to treatments that target mitotic spindle regulation. Here, we test this idea by inhibiting a subset of kinesin motor proteins involved in mitotic spindle control. KIF18A is required for proliferation of CIN cells derived from triple negative breast cancer or colorectal cancer tumors but is not required in near-diploid cells. Following KIF18A inhibition, CIN tumor cells exhibit mitotic delays, multipolar spindles, and increased cell death. Sensitivity to KIF18A knockdown is strongly correlated with centrosome fragmentation, which requires dynamic microtubules but does not depend on bipolar spindle formation or mitotic arrest. Our results indicate the altered spindle microtubule dynamics characteristic of CIN tumor cells can be exploited to reduce the proliferative capacity of CIN cells. Kinesin motor proteins are critical for maintaining mitotic spindle integrity, which is important for chromosome stability. Here, the authors show that the kinesin motor protein, KIF18A, permits the proliferation of chromosomally unstable cells and knockdown of KIF18A induces centrosome fragmentation. |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2aca43cc7a45dfc0f482c244f8260a6a https://pubmed.ncbi.nlm.nih.gov/33619254 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2aca43cc7a45dfc0f482c244f8260a6a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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