A novel β-catenin signaling pathway activated by IL-1β leads to the onset of epithelial-mesenchymal transition in breast cancer cells

Interieukin 1 beta has been associated with tumor development, invasiveness and metastasis in various types of cancer. However, the molecular mechanisms underlying this association have not been clearly elucidated. The present study is the first to show, in breast cancer cells, that an IL-1 beta/IL-1RI/beta-catenin signaling pathway induces beta-catenin accumulation due to GSK3 beta inactivation by Ala phosphorylation. Translocation to the nucleus of accumulated beta-catenin and formation of the TCF/Lef/beta-catenin complex induce sequential expression of c-MYC, CCDN1, SNAIL1 and MMP2, leading to up-regulation of proliferation, migration and invasion; all of the processes shown to be required, in cancerous cells, to initiate transition from a non-invading to an invasive phenotype. (C) 2014 Elsevier Ireland Ltd. All rights reserved.