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Loss of E-cadherin provides tolerance to centrosome amplification in epithelial cancer cells

Rhys, AD; Monteiro, P; Smith, C; Vaghela, M; Arnandis, T; Kato, T; Leitinger, B; ... Godinho, SA; + view all (2017) Loss of E-cadherin provides tolerance to centrosome amplification in epithelial cancer cells. Journal of Cell Biology , 2017 , Article jcb.201704102. 10.1083/jcb.201704102. Green open access

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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.

Type: Article
Title: Loss of E-cadherin provides tolerance to centrosome amplification in epithelial cancer cells
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1083/jcb.201704102
Publisher version: https://doi.org/10.1083/jcb.201704102
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Cytoskeleton, Cell Cycle and Division, Cancer
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > London Centre for Nanotechnology
URI: http://discovery.ucl.ac.uk/id/eprint/10039971
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