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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Line, Tumor
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Cell Movement
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Epithelial Cells / pathology*
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Extracellular Signal-Regulated MAP Kinases / physiology
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Homeodomain Proteins / physiology
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Humans
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MAP Kinase Signaling System
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Matrix Metalloproteinases / physiology
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Mesoderm / pathology*
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Mitogen-Activated Protein Kinase Kinases / physiology
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NF-kappa B / physiology*
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Neoplasm Invasiveness
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Pancreatic Neoplasms / pathology*
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Transcription Factors / physiology
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Transforming Growth Factor beta / pharmacology
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Tumor Necrosis Factor-alpha / pharmacology
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Zinc Finger E-box-Binding Homeobox 1
Substances
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Homeodomain Proteins
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NF-kappa B
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Transcription Factors
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Transforming Growth Factor beta
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Tumor Necrosis Factor-alpha
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ZEB1 protein, human
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Zinc Finger E-box-Binding Homeobox 1
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Extracellular Signal-Regulated MAP Kinases
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Mitogen-Activated Protein Kinase Kinases
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Matrix Metalloproteinases