Asymmetric Centriole Numbers at Spindle Poles Cause Chromosome Missegregation in Cancer
Chromosomal instability is a hallmark of cancer and correlates with the presence of extra centrosomes, which originate from centriole overduplication. Overduplicated centrioles lead to the formation of centriole rosettes, which mature into supernumerary centrosomes in the subsequent cell cycle. Whil...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717310768 |
| _version_ | 1817986367095832576 |
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| author | Marco R. Cosenza Anna Cazzola Annik Rossberg Nicole L. Schieber Gleb Konotop Elena Bausch Alla Slynko Tim Holland-Letz Marc S. Raab Taronish Dubash Hanno Glimm Sven Poppelreuther Christel Herold-Mende Yannick Schwab Alwin Krämer |
| author_facet | Marco R. Cosenza Anna Cazzola Annik Rossberg Nicole L. Schieber Gleb Konotop Elena Bausch Alla Slynko Tim Holland-Letz Marc S. Raab Taronish Dubash Hanno Glimm Sven Poppelreuther Christel Herold-Mende Yannick Schwab Alwin Krämer |
| author_sort | Marco R. Cosenza |
| collection | DOAJ |
| description | Chromosomal instability is a hallmark of cancer and correlates with the presence of extra centrosomes, which originate from centriole overduplication. Overduplicated centrioles lead to the formation of centriole rosettes, which mature into supernumerary centrosomes in the subsequent cell cycle. While extra centrosomes promote chromosome missegregation by clustering into pseudo-bipolar spindles, the contribution of centriole rosettes to chromosome missegregation is unknown. We used multi-modal imaging of cells with conditional centriole overduplication to show that mitotic rosettes in bipolar spindles frequently harbor unequal centriole numbers, leading to biased chromosome capture that favors binding to the prominent pole. This results in chromosome missegregation and aneuploidy. Rosette mitoses lead to viable offspring and significantly contribute to progeny production. We further show that centrosome abnormalities in primary human malignancies frequently consist of centriole rosettes. As asymmetric centriole rosettes generate mitotic errors that can be propagated, rosette mitoses are sufficient to cause chromosome missegregation in cancer. |
| first_indexed | 2024-04-14T00:09:17Z |
| format | Article |
| id | doaj.art-193775385eee40bca446c8e132ca6f3b |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-14T00:09:17Z |
| publishDate | 2017-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-193775385eee40bca446c8e132ca6f3b2022-12-22T02:23:25ZengElsevierCell Reports2211-12472017-08-012081906192010.1016/j.celrep.2017.08.005Asymmetric Centriole Numbers at Spindle Poles Cause Chromosome Missegregation in CancerMarco R. Cosenza0Anna Cazzola1Annik Rossberg2Nicole L. Schieber3Gleb Konotop4Elena Bausch5Alla Slynko6Tim Holland-Letz7Marc S. Raab8Taronish Dubash9Hanno Glimm10Sven Poppelreuther11Christel Herold-Mende12Yannick Schwab13Alwin Krämer14Clinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, 69120 Heidelberg, GermanyClinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, 69120 Heidelberg, GermanyClinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, 69120 Heidelberg, GermanyCell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, GermanyClinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, 69120 Heidelberg, GermanyClinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, 69120 Heidelberg, GermanyDivision of Biostatistics, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyDivision of Biostatistics, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyClinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, 69120 Heidelberg, GermanyDepartment of Translational Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyDepartment of Translational Oncology, National Center for Tumor Diseases (NCT) and German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyCarl Zeiss Application Center, 69120 Heidelberg, GermanyExperimental Neurosurgery, Department of Neurosurgery, University of Heidelberg, 69120 Heidelberg, GermanyCell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, GermanyClinical Cooperation Unit Molecular Hematology/Oncology, German Cancer Research Center (DKFZ) and Department of Internal Medicine V, University of Heidelberg, 69120 Heidelberg, GermanyChromosomal instability is a hallmark of cancer and correlates with the presence of extra centrosomes, which originate from centriole overduplication. Overduplicated centrioles lead to the formation of centriole rosettes, which mature into supernumerary centrosomes in the subsequent cell cycle. While extra centrosomes promote chromosome missegregation by clustering into pseudo-bipolar spindles, the contribution of centriole rosettes to chromosome missegregation is unknown. We used multi-modal imaging of cells with conditional centriole overduplication to show that mitotic rosettes in bipolar spindles frequently harbor unequal centriole numbers, leading to biased chromosome capture that favors binding to the prominent pole. This results in chromosome missegregation and aneuploidy. Rosette mitoses lead to viable offspring and significantly contribute to progeny production. We further show that centrosome abnormalities in primary human malignancies frequently consist of centriole rosettes. As asymmetric centriole rosettes generate mitotic errors that can be propagated, rosette mitoses are sufficient to cause chromosome missegregation in cancer.http://www.sciencedirect.com/science/article/pii/S2211124717310768chromosomal instabilitycentriolecentrosomePLK4STILmitosiscancermicrotubulemerotelychromosome missegregation |
| spellingShingle | Marco R. Cosenza Anna Cazzola Annik Rossberg Nicole L. Schieber Gleb Konotop Elena Bausch Alla Slynko Tim Holland-Letz Marc S. Raab Taronish Dubash Hanno Glimm Sven Poppelreuther Christel Herold-Mende Yannick Schwab Alwin Krämer Asymmetric Centriole Numbers at Spindle Poles Cause Chromosome Missegregation in Cancer Cell Reports chromosomal instability centriole centrosome PLK4 STIL mitosis cancer microtubule merotely chromosome missegregation |
| title | Asymmetric Centriole Numbers at Spindle Poles Cause Chromosome Missegregation in Cancer |
| title_full | Asymmetric Centriole Numbers at Spindle Poles Cause Chromosome Missegregation in Cancer |
| title_fullStr | Asymmetric Centriole Numbers at Spindle Poles Cause Chromosome Missegregation in Cancer |
| title_full_unstemmed | Asymmetric Centriole Numbers at Spindle Poles Cause Chromosome Missegregation in Cancer |
| title_short | Asymmetric Centriole Numbers at Spindle Poles Cause Chromosome Missegregation in Cancer |
| title_sort | asymmetric centriole numbers at spindle poles cause chromosome missegregation in cancer |
| topic | chromosomal instability centriole centrosome PLK4 STIL mitosis cancer microtubule merotely chromosome missegregation |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717310768 |
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