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Nat Cell Biol. 2014 Mar;16(3):245-54. doi: 10.1038/ncb2909. Epub 2014 Feb 9.

α-catenin acts as a tumour suppressor in E-cadherin-negative basal-like breast cancer by inhibiting NF-κB signalling.

Author information

  • 1Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center Houston Texas 77030 USA.
  • 21] Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center Houston Texas 77030 USA [2] Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine Houston Texas 77030 USA.
  • 3Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center Houston Texas 77030 USA.
  • 4Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center Houston Texas 77030 USA.
  • 51] Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center Houston Texas 77030 USA [2] Cancer Biology Program, Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston Houston Texas 77030 USA.

Abstract

Basal-like breast cancer is a highly aggressive tumour subtype associated with poor prognosis. Aberrant activation of NF-κB signalling is frequently found in triple-negative basal-like breast cancer cells, but the cause of this activation has remained elusive.Here we report that α-catenin functions as a tumour suppressor in E-cadherin-negative basal-like breast cancer cells by inhibiting NF-κB signalling. Mechanistically, α-catenin interacts with the IκBα protein, and stabilizes IκBα by inhibiting its ubiquitylation and its association with the proteasome. This stabilization in turn prevents nuclear localization of RelA and p50, leading to decreased expression of TNF-α, IL-8 and RelB. In human breast cancer, CTNNA1 expression is specifically downregulated in the basal-like subtype, correlates with clinical outcome and inversely correlates with TNF and RELB expression. Taken together, these results uncover a previously undescribed mechanism by which the NF-κB pathway is activated in E-cadherin-negative basal-like breast cancer.

PMID:
24509793
[PubMed - indexed for MEDLINE]
PMCID:
PMC3943677
Free PMC Article
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