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Loss of E-cadherin provides tolerance to centrosome amplification in epithelial cancer cells
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Rhys, Alexander D., Monteiro, Pedro, Smith, Christopher Matthew, Vaghela, Malti, Arnandis, Teresa, Kato, Takuya, Leitinger, Birgit, Sahai, Erik, McAinsh, Andrew D., Charras, Guillaume and Godinho, Susana A. (2017) Loss of E-cadherin provides tolerance to centrosome amplification in epithelial cancer cells. The Journal of Cell Biology, 217 (1). pp. 195-209. doi:10.1083/jcb.201704102
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Official URL: http://dx.doi.org/10.1083/jcb.201704102
Abstract
Centrosome amplification is a common feature of human tumors. To survive, cancer cells cluster extra centrosomes during mitosis, avoiding the detrimental effects of multipolar divisions. However, it is unclear whether clustering requires adaptation or is inherent to all cells. Here, we show that cells have varied abilities to cluster extra centrosomes. Epithelial cells are innately inefficient at clustering even in the presence of HSET/KIFC1, which is essential but not sufficient to promote clustering. The presence of E-cadherin decreases cortical contractility during mitosis through a signaling cascade leading to multipolar divisions, and its knockout promotes clustering and survival of cells with multiple centrosomes. Cortical contractility restricts centrosome movement at a minimal distance required for HSET/KIFC1 to exert its function, highlighting a biphasic model for centrosome clustering. In breast cancer cell lines, increased levels of centrosome amplification are accompanied by efficient clustering and loss of E-cadherin, indicating that this is an important adaptation mechanism to centrosome amplification in cancer.
| Item Type: | Journal Article | ||||||||||||
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| Subjects: | Q Science > QH Natural history | ||||||||||||
| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences | ||||||||||||
| Library of Congress Subject Headings (LCSH): | Cancer cells, Centrosomes, Cadherins, Cell division, Epithelial cells | ||||||||||||
| Journal or Publication Title: | The Journal of Cell Biology | ||||||||||||
| Publisher: | Rockefeller University Press | ||||||||||||
| ISSN: | 0021-9525 | ||||||||||||
| Official Date: | 13 November 2017 | ||||||||||||
| Dates: |
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| Date of first compliant deposit: | 27 February 2018 | ||||||||||||
| Volume: | 217 | ||||||||||||
| Number: | 1 | ||||||||||||
| Page Range: | pp. 195-209 | ||||||||||||
| DOI: | 10.1083/jcb.201704102 | ||||||||||||
| Status: | Peer Reviewed | ||||||||||||
| Publication Status: | Published | ||||||||||||
| Access rights to Published version: | Open Access | ||||||||||||
| RIOXX Funder/Project Grant: |
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