[HTML][HTML] Downregulation of TRAF2 mediates NIK-induced pancreatic cancer cell proliferation and tumorigenicity

H Döppler, GY Liou, P Storz - PLoS One, 2013 - journals.plos.org
H Döppler, GY Liou, P Storz
PLoS One, 2013journals.plos.org
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) …
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.
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