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Nat Commun. 2016 Dec 22;7:13874. doi: 10.1038/ncomms13874.

p120-catenin prevents multinucleation through control of MKLP1-dependent RhoA activity during cytokinesis.

Author information

1
Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
2
Tumour Cell Biology Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
3
Department of Molecular Cell Biology, Leiden University Medical Center, Einthovenweg 20, 2300 RC Leiden, The Netherlands.
4
Department of Internal Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
5
Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, UK.
6
Department of Oncology, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
7
Cambridge Experimental Cancer Medicine Centre and NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
8
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.

Abstract

Spatiotemporal activation of RhoA and actomyosin contraction underpins cellular adhesion and division. Loss of cell-cell adhesion and chromosomal instability are cardinal events that drive tumour progression. Here, we show that p120-catenin (p120) not only controls cell-cell adhesion, but also acts as a critical regulator of cytokinesis. We find that p120 regulates actomyosin contractility through concomitant binding to RhoA and the centralspindlin component MKLP1, independent of cadherin association. In anaphase, p120 is enriched at the cleavage furrow where it binds MKLP1 to spatially control RhoA GTPase cycling. Binding of p120 to MKLP1 during cytokinesis depends on the N-terminal coiled-coil domain of p120 isoform 1A. Importantly, clinical data show that loss of p120 expression is a common event in breast cancer that strongly correlates with multinucleation and adverse patient survival. In summary, our study identifies p120 loss as a driver event of chromosomal instability in cancer.

PMID:
28004812
PMCID:
PMC5192218
DOI:
10.1038/ncomms13874
[Indexed for MEDLINE]
Free PMC Article

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