PMID- 23301098
OWN - NLM
STAT- MEDLINE
DCOM- 20130820
LR  - 20231213
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 1
DP  - 2013
TI  - Downregulation of TRAF2 mediates NIK-induced pancreatic cancer cell proliferation 
      and tumorigenicity.
PG  - e53676
LID - 10.1371/journal.pone.0053676 [doi]
LID - e53676
AB  - BACKGROUND: Increased levels of NF-kappaB are hallmarks of pancreatic ductal 
      adenocarcinoma (PDAC) and both classical and alternative NF-kappaB 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-kappaB 
      activity in PDAC cell lines. Increased activity of the p52/RelB NF-kappaB complex is 
      mediated through stabilization and activation of NF-kappaB-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-kappaB2 pathway regulates 
      PDAC cell tumorigenicity and could be a valuable target for therapy of this 
      cancer.
FAU - Doppler, Heike
AU  - Doppler H
AD  - Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Mayo 
      Clinic, Jacksonville, Florida, United States of America.
FAU - Liou, Geou-Yarh
AU  - Liou GY
FAU - Storz, Peter
AU  - Storz P
LA  - eng
GR  - R21 CA135102/CA/NCI NIH HHS/United States
GR  - P50CA102701/CA/NCI NIH HHS/United States
GR  - R01 CA140182/CA/NCI NIH HHS/United States
GR  - P50 CA102701/CA/NCI NIH HHS/United States
GR  - CA140182/CA/NCI NIH HHS/United States
GR  - CA135102/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130103
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (NF-kappa B p52 Subunit)
RN  - 0 (NFKB2 protein, human)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Thiazoles)
RN  - 9002-18-0 (Agar)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - EUY85H477I (thiazolyl blue)
SB  - IM
MH  - Agar/chemistry
MH  - Carcinoma, Pancreatic Ductal/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Nucleus/metabolism
MH  - Cell Proliferation
MH  - Chemotaxis
MH  - Down-Regulation
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - NF-kappa B p52 Subunit/*metabolism
MH  - Pancreatic Neoplasms/*metabolism
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Protein Binding
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - TNF Receptor-Associated Factor 2/*metabolism
MH  - Tetrazolium Salts/pharmacology
MH  - Thiazoles/pharmacology
MH  - NF-kappaB-Inducing Kinase
PMC - PMC3536768
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/01/10 06:00
MHDA- 2013/08/21 06:00
PMCR- 2013/01/03
CRDT- 2013/01/10 06:00
PHST- 2012/07/26 00:00 [received]
PHST- 2012/12/03 00:00 [accepted]
PHST- 2013/01/10 06:00 [entrez]
PHST- 2013/01/10 06:00 [pubmed]
PHST- 2013/08/21 06:00 [medline]
PHST- 2013/01/03 00:00 [pmc-release]
AID - PONE-D-12-22714 [pii]
AID - 10.1371/journal.pone.0053676 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(1):e53676. doi: 10.1371/journal.pone.0053676. Epub 2013 Jan 3.