NF-kappaB promotes epithelial-mesenchymal transition, migration and invasion of pancreatic carcinoma cells.
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.
Maier
Harald J
HJ
Institute of Physiological Chemistry, University of Ulm, Germany.
Schmidt-Strassburger
Uta
U
Huber
Margit A
MA
Wiedemann
Eva M
EM
Beug
Hartmut
H
Wirth
Thomas
T
D045744:Cell Line, Tumor; D002465:Cell Movement; D004847:Epithelial Cells / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D018398:Homeodomain Proteins / Q000502:physiology; D006801:Humans; D020935:MAP Kinase Signaling System; D020782:Matrix Metalloproteinases / Q000502:physiology; D008648:Mesoderm / Q000473:pathology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D016328:NF-kappa B / Q000502:physiology*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000473:pathology*; D014157:Transcription Factors / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000071799:Zinc Finger E-box-Binding Homeobox 1
D018398:Homeodomain Proteins; D016328:NF-kappa B; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D020782:Matrix Metalloproteinases