title: Downregulation of TRAF2 mediates NIK-induced pancreatic cancer cell proliferation and tumorigenicity.
abstract: BACKGROUND
  Increased levels of NF-κB are hallmarks of pancreatic ductal adenocarcinoma (PDAC) and both classical and alternative NF-κB activation pathways have been implicated.
  
  
  RESULTS
  Here we show that activation of the alternative pathway is a source for the high basal NF-κB activity in PDAC cell lines. Increased activity of the p52/RelB NF-κB complex is mediated through stabilization and activation of NF-κB-inducing kinase (NIK). We identify proteasomal downregulation of TNF receptor-associated factor 2 (TRAF2) as a mechanism by which levels of active NIK are increased in PDAC cell lines. Such upregulation of NIK expression and activity levels relays to increased proliferation and anchorage-independent growth, but not migration or survival of PDAC cells.
  
  
  CONCLUSIONS
  Rapid growth is one characteristic of pancreatic cancer. Our data indicates that the TRAF2/NIK/NF-κB2 pathway regulates PDAC cell tumorigenicity and could be a valuable target for therapy of this cancer.
authors.affiliation: Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo Clinic, Jacksonville, Florida, United States of America.
authors.forename: Heike
authors.initials: H
authors.lastname: Döppler
authors.forename: Geou-Yarh
authors.initials: GY
authors.lastname: Liou
authors.forename: Peter
authors.initials: P
authors.lastname: Storz
mesh_terms: D000362:Agar / Q000737:chemistry; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002633:Chemotaxis; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D052003:NF-kappa B p52 Subunit / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism*; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D000362:Agar; D052003:NF-kappa B p52 Subunit; D046988:Proteasome Endopeptidase Complex; D017346:Protein Serine-Threonine Kinases; D047992:TNF Receptor-Associated Factor 2; D013778:Tetrazolium Salts; D013844:Thiazoles; D000097782:NF-kappaB-Inducing Kinase; C498206:NFKB2 protein, human; C022616:thiazolyl blue