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

被引:197
作者
Maier, Harald J. [1 ]
Schmidt-Strassburger, Uta [1 ]
Huber, Margit A. [2 ,3 ]
Wiedemann, Eva M. [3 ]
Beug, Hartmut [3 ]
Wirth, Thomas [1 ]
机构
[1] Univ Ulm, Inst Physiol Chem, D-89081 Ulm, Germany
[2] Univ Ulm, Dept Dermatol & Allerg Dis, D-89081 Ulm, Germany
[3] Res Inst Mol Pathol, A-1030 Vienna, Austria
关键词
NF-kappa B; Epithelial-mesenchymal transition; Pancreatic adenocarcinoma; Tumour progression; Cell migration; Cell invasion; GROWTH-FACTOR; SNAIL TRANSCRIPTION; GENE-EXPRESSION; TUMOR-GROWTH; ACTIVATION; CANCER; ALPHA; BETA; INFLAMMATION; ADENOCARCINOMA;
D O I
10.1016/j.canlet.2010.03.003
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:214 / 228
页数:15
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[1]   NF-κB activation in Esophageal adenocarcinoma -: Relationship to Barrett's metaplasia, survival, and response to neoadjuvant chemoradiotherapy [J].
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O'Riordan, J ;
Windle, HJ ;
Carton, E ;
Ravi, N ;
Kelleher, D ;
Reynolds, JV .
ANNALS OF SURGERY, 2004, 239 (04) :491-500
[2]   Glycogen synthase kinase-3 is an endogenous inhibitor of snail transcription: implications for the epithelial-mesenchymal transition [J].
Bachelder, RE ;
Yoon, SO ;
Franci, C ;
de Herreros, AG ;
Mercurio, AM .
JOURNAL OF CELL BIOLOGY, 2005, 168 (01) :29-33
[3]   Regulation of Snail transcription during epithelial to mesenchymal transition of tumor cells [J].
Barberà, MJ ;
Puig, I ;
Domínguez, D ;
Julien-Grille, S ;
Guaita-Esteruelas, S ;
Peiró, S ;
Baulida, J ;
Francí, C ;
Dedhar, S ;
Larue, L ;
de Herreros, AG .
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[4]   Tumor necrosis factor-α stimulates the epithelial-to-mesenchymal transition of human colonic organoids [J].
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Mercurio, AM .
MOLECULAR BIOLOGY OF THE CELL, 2003, 14 (05) :1790-1800
[5]   An essential role for NF-kappa B in preventing TNF-alpha-induced cell death [J].
Beg, AA ;
Baltimore, D .
SCIENCE, 1996, 274 (5288) :782-784
[6]   Matrix metalloproteinases and their role in pancreatic cancer: A review of preclinical studies and clinical trials [J].
Mark Bloomston ;
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[7]   NF-κB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells:: potential involvement of ZEB-1 and ZEB-2 [J].
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Clare, S. E. ;
Morimiya, A. ;
Badve, S. ;
Nakshatri, H. .
ONCOGENE, 2007, 26 (05) :711-724
[8]   Tumor-derived tumor necrosis factor-alpha promotes progression and epithelial-mesenchymal transition in renal cell carcinoma cells [J].
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Deng, Ming-Wei ;
Wu, Yu-Hsin ;
Sung, Jung-Sung ;
Cha, Tai-Lung ;
Sun, Guang-Huan .
CANCER SCIENCE, 2008, 99 (05) :905-913
[9]   Gene expression profiles identify epithelial-to-mesenchymal transition and activation of nuclear factor-κB signaling as characteristics of a high-risk head and neck squamous cell carcinoma [J].
Chung, Christine H. ;
Parker, Joe S. ;
Ely, Kim ;
Carter, Jesse ;
Yi, Yajun ;
Murphy, Barbara A. ;
Ang, K. Man ;
El-Naggar, Adel K. ;
Zanation, Adam M. ;
Cmelak, Anthony J. ;
Levy, Shawn ;
Slebos, Robbert J. ;
Yarbrough, Wendell G. .
CANCER RESEARCH, 2006, 66 (16) :8210-8218
[10]   Activation of NF-κB via the IκB kinase complex is both essential and sufficient for proinflammatory gene expression in primary endothelial cells [J].
Denk, A ;
Goebeler, M ;
Schmid, S ;
Berberich, I ;
Ritz, O ;
Lindemann, D ;
Ludwig, S ;
Wirth, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (30) :28451-28458