NF-[kappa]B promotes epithelial-mesenchymal transition, migration and invasion of pancreatic carcinoma cells

The transcription factor NF-κB is constitutively active in pancreatic adenocarcinoma. Here we explore the contribution of NF-κB to the malignant phenotype of pancreatic cancer cells in addition to its anti-apoptotic role. Block of NF-κB signalling by non-destructible IκBα rendered cells resistant to TGF-β-induced epithelial-mesenchymal transition (EMT). In contrast, NF-κB activation by TNF-α 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-β signalling. Functional assays demonstrated reduced or strongly enhanced migration and invasion upon NF-κB inhibition or activation, respectively.