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Julien S, Puig I, Caretti E, Bonaventure J, Nelles L, van Roy F, Dargemont C, Garcia de Herreros A, Bellacosa A, Larue L
Activation of NF-kappa B by Akt upregulates Snail expression and induces epithelium mesenchyme transition
Oncogene (2007) 26:7445-7456.
Carcinoma progression is associated with the loss of epithelial features, and the acquisition of mesenchymal characteristics and invasive properties by tumour cells. The loss of cell-cell contacts may be the. first step of the epithelium mesenchyme transition (EMT) and involves the functional inactivation of the cell-cell adhesion molecule E-cadherin. Repression of E-cadherin expression by the transcription factor Snail is a central event during the loss of epithelial phenotype. Akt kinase activation is frequent in human carcinomas, and Akt regulates various cellular mechanisms including EMT. Here, we show that Snail activation and consequent repression of E- cadherin may depend on AKT-mediated nuclear factor-kappa B (NF-kappa B) activation, and that NF-kappa B induces Snail expression. Expression of the NF-kappa B subunit p65 is suficient for EMT induction, validating this signalling module during EMT. NF-kappa B pathway activation is associated with tumour progression and metastasis of several human tumour types; E-cadherin acts as a metastasis suppressor protein. Thus, this signalling and transcriptional network linking AKT, NF-kappa B, Snail and E-cadherin during EMT is a potential target for antimetastatic therapeutics.
Publication Date: 2007-11-01.
Last updated on Monday, May 04, 2020