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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

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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
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:
DateEvent
13 November 2017Published
10 October 2017Accepted
13 April 2017Submitted
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:
Project/Grant IDRIOXX Funder NameFunder ID
UNSPECIFIEDHuman Frontier Science Programhttp://dx.doi.org/10.13039/100004412
UNSPECIFIEDCancer Research UKhttp://dx.doi.org/10.13039/501100000289
MR/M010414/1[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265

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