Author(s): Maier HJ, SchmidtStrassburger U, Huber MA, Wiedemann EM, Beug H,
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Abstract The transcription factor NF-kappaB is constitutively active in pancreatic adenocarcinoma. Here we explore the contribution of NF-kappaB to the malignant phenotype of pancreatic cancer cells in addition to its anti-apoptotic role. Block of NF-kappaB signalling by non-destructible IkappaBalpha rendered cells resistant to TGF-beta-induced epithelial-mesenchymal transition (EMT). In contrast, NF-kappaB 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-kappaB inhibition or activation, respectively. 2010 Elsevier Ireland Ltd. All rights reserved.
This article was published in Cancer Lett
and referenced in Pancreatic Disorders & Therapy