NF-κB promotes epithelial-mesenchynmal transition, migration and invasion of pancreatic carcinoma cells

The transcription factor NF-kappa B is constitutively active in pancreatic adenocarcinoma. Here we explore the contribution of NF-kappa B to the malignant phenotype of pancreatic cancer cells in addition to its anti-apoptotic role. Block of NF-kappa B signalling by non-destructible ham rendered cells resistant to TGF-beta-induced epithelial-mesenchymal transition (EMT). In contrast, NF-kappa B activation by TNF-alpha or expression of constitutively active IKK2 induced an EMT-phenotype with up-regulation of vimentin and ZEB1, and down-regulation of E-cadherin. EMT could also be induced in cells with defective TGF-beta signalling. Functional assays demonstrated reduced or strongly enhanced migration and invasion upon NF-kappa B inhibition or activation, respectively. (C) 2010 Elsevier Ireland Ltd. All rights reserved.