Loss of Par3 promotes breast cancer metastasis by compromising cell-cell cohesion

Xue, B., Krishnamurthy, K., Allred, D. C., Muthuswamy, S. K. (2013) Loss of Par3 promotes breast cancer metastasis by compromising cell-cell cohesion. Nature Cell Biology, 15 (2). pp. 189-200. ISSN 1465-7392

Abstract

The mechanisms by which tumour cells metastasize and the role that cell polarity proteins play in this process are not well understood. We report that partitioning defective protein 3 (Par3) is dysregulated in metastasis in human breast cancer, and is associated with a higher tumour grade and ErbB2-positive status. Downregulation of Par3 cooperated with ErbB2 to induce cell invasion and metastasis in vivo. Interestingly, the metastatic behaviour was not associated with an overt mesenchymal phenotype. However, loss of Par3 inhibited E-cadherin junction stability, disrupted membrane and actin dynamics at cell-cell junctions and decreased cell-cell cohesion in a manner dependent on the Tiam1/Rac-GTP pathway. Inhibition of this pathway restored E-cadherin junction stability and blocked invasive behaviour of cells lacking Par3, suggesting that loss of Par3 promotes metastatic behaviour of ErbB2-induced tumour epithelial cells by decreasing cell-cell cohesion.

Item Type:	Paper
Subjects:	diseases & disorders > cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing diseases & disorders > cancer > cancer types > breast cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function diseases & disorders > cancer > cancer types
CSHL Authors:	Krishnamurthy, Kannan Muthuswamy, Senthil K. Xue, Bin
Communities:	CSHL Cancer Center Program > Signal Transduction CSHL Cancer Center Shared Resources > Animal Services CSHL Cancer Center Shared Resources > Flow Cytometry Service CSHL Cancer Center Shared Resources > Mass Spectrometry Service CSHL Cancer Center Shared Resources > Microscopy Service CSHL Cancer Center Shared Resources > Proteomics Service CSHL labs > Muthuswamy lab
Depositing User:	Matt Covey
Date:	2013
Date Deposited:	22 May 2013 16:46
Last Modified:	19 Jul 2021 15:23
PMCID:	PMC4577246
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/28303

Actions (login required)

Administrator's edit/view item