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

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dc.contributor.author Kovac, Bianca
dc.contributor.author Makela, Tomi P.
dc.contributor.author Vallenius, Tea
dc.date.accessioned 2018-07-12T10:53:01Z
dc.date.available 2018-07-12T10:53:01Z
dc.date.issued 2018-05-09
dc.identifier.citation 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
dc.identifier.other PURE: 109386561
dc.identifier.other PURE UUID: 9b2e36f7-7483-49dd-ab6d-4291e62a867d
dc.identifier.other WOS: 000431757400053
dc.identifier.other Scopus: 85046832281
dc.identifier.other ORCID: /0000-0002-4869-8044/work/46650109
dc.identifier.uri http://hdl.handle.net/10138/237101
dc.description.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. en
dc.format.extent 20
dc.language.iso eng
dc.relation.ispartof PLoS One
dc.rights unspecified
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject GROWTH-FACTOR-BETA
dc.subject EPITHELIAL-MESENCHYMAL TRANSITION
dc.subject CELL-CELL JUNCTIONS
dc.subject ALPHA-ACTININ
dc.subject GENE-EXPRESSION
dc.subject INDEPENDENT MANNER
dc.subject ADHERENS JUNCTIONS
dc.subject OVARIAN-CANCER
dc.subject TGF-BETA
dc.subject INVASION
dc.subject 3111 Biomedicine
dc.subject 3122 Cancers
dc.title Increased alpha-actinin-1 destabilizes E-cadherin-based adhesions and associates with poor prognosis in basal-like breast cancer en
dc.type Article
dc.contributor.organization Research Programs Unit
dc.contributor.organization Helsinki Institute of Life Science HiLIFE, Joint Activities
dc.contributor.organization Doctoral Programme in Integrative Life Science
dc.contributor.organization Medicum
dc.contributor.organization Mäkelä Lab
dc.contributor.organization Helsinki Institute of Life Science HiLIFE
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.1371/journal.pone.0196986
dc.relation.issn 1932-6203
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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