Increased alpha-actinin-1 destabilizes E-cadherin-based adhesions and associates with poor prognosis in basal-like breast cancer

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Kovac , B , Makela , T P & Vallenius , T 2018 , ' Increased alpha-actinin-1 destabilizes E-cadherin-based adhesions and associates with poor prognosis in basal-like breast cancer ' , PLoS One , vol. 13 , no. 5 , 0196986 . https://doi.org/10.1371/journal.pone.0196986

Title: Increased alpha-actinin-1 destabilizes E-cadherin-based adhesions and associates with poor prognosis in basal-like breast cancer
Author: Kovac, Bianca; Makela, Tomi P.; Vallenius, Tea
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Helsinki Institute of Life Science HiLIFE, Joint Activities
University of Helsinki, Research Programs Unit
Date: 2018-05-09
Language: eng
Number of pages: 20
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/237101
Abstract: The controlled formation and stabilization of E-cadherin-based adhesions is vital for epithelial integrity. This requires co-operation between the E-cadherin-based adhesions and the associated actin cytoskeleton. In cancer, this co-operation often fails, predisposing cells to migration through molecular mechanisms that have only been partially characterized. Here, we demonstrate that the actin filament cross-linker alpha-actinin-1 is frequently increased in human breast cancer. In mammary epithelial cells, the increased alpha-actinin-1 levels promote cell migration and induce disorganized acini-like structures in Matrigel. This is accompanied by a major reorganization of the actin cytoskeleton and the associated E-cadherin-based adhesions. Increased expression of alpha-actinin-1 is particularly noted in basal-like breast cancer cell lines, and in breast cancer patients it associates with poor prognosis in basal-like subtypes. Downregulation of alpha-actinin-1 in E-cadherin expressing basal-like breast cancer cells demonstrate that alpha-actinin-1-assembled actin fibers destabilize E-cadherin-based adhesions. Taken together, these results indicate that increased alpha-actinin-1 expression destabilizes E-cadherin-based adhesions, which is likely to promote the migratory potential of breast cancer cells. Furthermore, our results identify alpha-actinin-1 as a candidate prognostic biomarker in basal-like breast cancer.
Subject: GROWTH-FACTOR-BETA
EPITHELIAL-MESENCHYMAL TRANSITION
CELL-CELL JUNCTIONS
ALPHA-ACTININ
GENE-EXPRESSION
INDEPENDENT MANNER
ADHERENS JUNCTIONS
OVARIAN-CANCER
TGF-BETA
INVASION
3111 Biomedicine
3122 Cancers
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