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.

METHODOLOGY/PRINCIPAL FINDINGS:

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/SIGNIFICANCE:

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: Heike Döppler, Geou-Yarh Liou, Peter Storz
• Journal: PloS one (PLoS One) Vol. 8 Issue 1 Pg. e53676 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23301098 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B p52 Subunit
• NFKB2 protein, human
• TNF Receptor-Associated Factor 2
• Tetrazolium Salts
• Thiazoles
• Agar
• Protein Serine-Threonine Kinases
• NF-kappa B kinase
• Proteasome Endopeptidase Complex
• thiazolyl blue

Topics

• Agar (chemistry)
• Carcinoma, Pancreatic Ductal (metabolism)
• Cell Line, Tumor
• Cell Movement
• Cell Nucleus (metabolism)
• Cell Proliferation
• Chemotaxis
• Down-Regulation
• Gene Expression Regulation, Neoplastic
• Humans
• NF-kappa B p52 Subunit (metabolism)
• Pancreatic Neoplasms (metabolism)
• Proteasome Endopeptidase Complex (metabolism)
• Protein Binding
• Protein Serine-Threonine Kinases (metabolism)
• TNF Receptor-Associated Factor 2 (metabolism)
• Tetrazolium Salts (pharmacology)
• Thiazoles (pharmacology)