α-catenin acts as a tumour suppressor in E-cadherin-negative basal-like breast cancer by inhibiting NF-κB signalling
Menée in vitro, in vivo et à partir de données issues du projet "The Cancer Genome Atlas", cette étude met en évidence des mécanismes par lesquels, en inhibant la signalisation NF-κB, l'alpha-caténine joue un rôle de suppresseur de tumeurs dans les cancers du sein "basal-like" n'exprimant pas l'E-cadhérine
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.