Background

Increased levels of NF-¿B are hallmarks of pancreatic ductal adenocarcinoma (PDAC) and both classical and alternative NF-¿B 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-¿B activity in PDAC cell lines. Increased activity of the p52/RelB NF-¿B complex is mediated through stabilization and activation of NF-¿B-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-¿B2 pathway regulates PDAC cell tumorigenicity and could be a valuable target for therapy of this cancer.

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