Downregulation of TRAF2 Mediates NIK-Induced Pancreatic Cancer Cell Proliferation and Tumorigenicity

Heike Döppler, Geou Yarh Liou, Peter Storz

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere53676
JournalPLoS One
Volume8
Issue number1
DOIs
StatePublished - Jan 3 2013

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TNF Receptor-Associated Factor 2
pancreatic neoplasms
Cell proliferation
adenocarcinoma
Pancreatic Neoplasms
cell proliferation
phosphotransferases (kinases)
Adenocarcinoma
Phosphotransferases
Down-Regulation
Cell Proliferation
receptors
Chemical activation
Cells
cell lines
Cell Line
Growth
Stabilization
Up-Regulation
neoplasm cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Downregulation of TRAF2 Mediates NIK-Induced Pancreatic Cancer Cell Proliferation and Tumorigenicity. / Döppler, Heike; Liou, Geou Yarh; Storz, Peter.

In: PLoS One, Vol. 8, No. 1, e53676, 03.01.2013.

Research output: Contribution to journalArticle

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