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

Xue, B., Krishnamurthy, K., Allred, D. C., Muthuswamy, S. K. (December 2012) Loss of Par3 promotes breast cancer metastasis by compromising cell-cell cohesion. Nat Cell Biol. ISSN 1476-4679 (Electronic)1465-7392 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/23263278
DOI: 10.1038/ncb2663

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
diseases & disorders
diseases & disorders > cancer > cancer types > breast cancer
CSHL Authors:
Communities: CSHL labs > Muthuswamy lab
Depositing User: Matt Covey
Date: 23 December 2012
Date Deposited: 17 Jan 2013 20:15
Last Modified: 17 Jan 2013 20:15
PMCID: NLM
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27084

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