Differential sensitivity of Glioma stem cells to Aurora kinase A inhibitors: Implications for stem cell mitosis and centrosome dynamics
Glioma stem-cell-like cells are considered to be responsible for treatment resistance and tumour recurrence following chemo-radiation in glioblastoma patients, but specific targets by which to kill the cancer stem cell population remain elusive. A characteristic feature of stem cells is their abilit...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-07-01
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| Series: | Stem Cell Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1873506114000609 |
| _version_ | 1818542366219304960 |
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| author | Mariella Mannino Natividad Gomez-Roman Helfrid Hochegger Anthony J. Chalmers |
| author_facet | Mariella Mannino Natividad Gomez-Roman Helfrid Hochegger Anthony J. Chalmers |
| author_sort | Mariella Mannino |
| collection | DOAJ |
| description | Glioma stem-cell-like cells are considered to be responsible for treatment resistance and tumour recurrence following chemo-radiation in glioblastoma patients, but specific targets by which to kill the cancer stem cell population remain elusive. A characteristic feature of stem cells is their ability to undergo both symmetric and asymmetric cell divisions. In this study we have analysed specific features of glioma stem cell mitosis. We found that glioma stem cells appear to be highly prone to undergo aberrant cell division and polyploidization. Moreover, we discovered a pronounced change in the dynamic of mitotic centrosome maturation in these cells. Accordingly, glioma stem cell survival appeared to be strongly dependent on Aurora A activity. Unlike differentiated cells, glioma stem cells responded to moderate Aurora A inhibition with spindle defects, polyploidization and a dramatic increase in cellular senescence, and were selectively sensitive to Aurora A and Plk1 inhibitor treatment. Our study proposes inhibition of centrosomal kinases as a novel strategy to selectively target glioma stem cells. |
| first_indexed | 2024-12-11T22:21:08Z |
| format | Article |
| id | doaj.art-df5fc42c115a413ab12d6373d3bc1a19 |
| institution | Directory Open Access Journal |
| issn | 1873-5061 1876-7753 |
| language | English |
| last_indexed | 2024-12-11T22:21:08Z |
| publishDate | 2014-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Stem Cell Research |
| spelling | doaj.art-df5fc42c115a413ab12d6373d3bc1a192022-12-22T00:48:26ZengElsevierStem Cell Research1873-50611876-77532014-07-0113113514310.1016/j.scr.2014.05.001Differential sensitivity of Glioma stem cells to Aurora kinase A inhibitors: Implications for stem cell mitosis and centrosome dynamicsMariella Mannino0Natividad Gomez-Roman1Helfrid Hochegger2Anthony J. Chalmers3Genome Damage and Stability Centre, University of Sussex, Brighton BN19RQ, UKInstitute of Cancer Sciences, University of Glasgow, Glasgow G12 8QQ, UKGenome Damage and Stability Centre, University of Sussex, Brighton BN19RQ, UKInstitute of Cancer Sciences, University of Glasgow, Glasgow G12 8QQ, UKGlioma stem-cell-like cells are considered to be responsible for treatment resistance and tumour recurrence following chemo-radiation in glioblastoma patients, but specific targets by which to kill the cancer stem cell population remain elusive. A characteristic feature of stem cells is their ability to undergo both symmetric and asymmetric cell divisions. In this study we have analysed specific features of glioma stem cell mitosis. We found that glioma stem cells appear to be highly prone to undergo aberrant cell division and polyploidization. Moreover, we discovered a pronounced change in the dynamic of mitotic centrosome maturation in these cells. Accordingly, glioma stem cell survival appeared to be strongly dependent on Aurora A activity. Unlike differentiated cells, glioma stem cells responded to moderate Aurora A inhibition with spindle defects, polyploidization and a dramatic increase in cellular senescence, and were selectively sensitive to Aurora A and Plk1 inhibitor treatment. Our study proposes inhibition of centrosomal kinases as a novel strategy to selectively target glioma stem cells.http://www.sciencedirect.com/science/article/pii/S1873506114000609 |
| spellingShingle | Mariella Mannino Natividad Gomez-Roman Helfrid Hochegger Anthony J. Chalmers Differential sensitivity of Glioma stem cells to Aurora kinase A inhibitors: Implications for stem cell mitosis and centrosome dynamics Stem Cell Research |
| title | Differential sensitivity of Glioma stem cells to Aurora kinase A inhibitors: Implications for stem cell mitosis and centrosome dynamics |
| title_full | Differential sensitivity of Glioma stem cells to Aurora kinase A inhibitors: Implications for stem cell mitosis and centrosome dynamics |
| title_fullStr | Differential sensitivity of Glioma stem cells to Aurora kinase A inhibitors: Implications for stem cell mitosis and centrosome dynamics |
| title_full_unstemmed | Differential sensitivity of Glioma stem cells to Aurora kinase A inhibitors: Implications for stem cell mitosis and centrosome dynamics |
| title_short | Differential sensitivity of Glioma stem cells to Aurora kinase A inhibitors: Implications for stem cell mitosis and centrosome dynamics |
| title_sort | differential sensitivity of glioma stem cells to aurora kinase a inhibitors implications for stem cell mitosis and centrosome dynamics |
| url | http://www.sciencedirect.com/science/article/pii/S1873506114000609 |
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