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

Robert A.H. van de Ven, Jolien S. de Groot, Danielle Park, Robert van Domselaar, Danielle de Jong, Karoly Szuhai, Elsken van der Wall, Oscar M. Rueda, H. Raza Ali, Carlos Caldas, Paul J. van Diest, Martin W. Hetzer, Erik Sahai and Patrick W.B. Derksen ()
Additional contact information
Robert A.H. van de Ven: University Medical Center Utrecht
Jolien S. de Groot: University Medical Center Utrecht
Danielle Park: Tumour Cell Biology Laboratory, Cancer Research UK London Research Institute
Robert van Domselaar: University Medical Center Utrecht
Danielle de Jong: Leiden University Medical Center
Karoly Szuhai: Leiden University Medical Center
Elsken van der Wall: University Medical Center Utrecht
Oscar M. Rueda: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre
H. Raza Ali: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre
Carlos Caldas: Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre
Paul J. van Diest: University Medical Center Utrecht
Martin W. Hetzer: Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies
Erik Sahai: Tumour Cell Biology Laboratory, Cancer Research UK London Research Institute
Patrick W.B. Derksen: University Medical Center Utrecht

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13874

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