Downregulation of TRAF2 mediates NIK-induced pancreatic cancer cell proliferation and tumorigenicity.
Increased levels of NF-κB are hallmarks of pancreatic ductal adenocarcinoma (PDAC) and both classical and alternative NF-κB activation pathways have been implicated.Here we show that activation of the alternative pathway is a source for the high basal NF-κB activity in PDAC cell lines. Increased act...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3536768?pdf=render |
| _version_ | 1818452269157318656 |
|---|---|
| author | Heike Döppler Geou-Yarh Liou Peter Storz |
| author_facet | Heike Döppler Geou-Yarh Liou Peter Storz |
| author_sort | Heike Döppler |
| collection | DOAJ |
| description | Increased levels of NF-κB are hallmarks of pancreatic ductal adenocarcinoma (PDAC) and both classical and alternative NF-κB activation pathways have been implicated.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.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. |
| first_indexed | 2024-12-14T21:20:24Z |
| format | Article |
| id | doaj.art-1a8535ce700346da9c746bcf8b3c267e |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T21:20:24Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1a8535ce700346da9c746bcf8b3c267e2022-12-21T22:46:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0181e5367610.1371/journal.pone.0053676Downregulation of TRAF2 mediates NIK-induced pancreatic cancer cell proliferation and tumorigenicity.Heike DöpplerGeou-Yarh LiouPeter StorzIncreased levels of NF-κB are hallmarks of pancreatic ductal adenocarcinoma (PDAC) and both classical and alternative NF-κB activation pathways have been implicated.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.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.http://europepmc.org/articles/PMC3536768?pdf=render |
| spellingShingle | Heike Döppler Geou-Yarh Liou Peter Storz Downregulation of TRAF2 mediates NIK-induced pancreatic cancer cell proliferation and tumorigenicity. PLoS ONE |
| title | Downregulation of TRAF2 mediates NIK-induced pancreatic cancer cell proliferation and tumorigenicity. |
| title_full | Downregulation of TRAF2 mediates NIK-induced pancreatic cancer cell proliferation and tumorigenicity. |
| title_fullStr | Downregulation of TRAF2 mediates NIK-induced pancreatic cancer cell proliferation and tumorigenicity. |
| title_full_unstemmed | Downregulation of TRAF2 mediates NIK-induced pancreatic cancer cell proliferation and tumorigenicity. |
| title_short | Downregulation of TRAF2 mediates NIK-induced pancreatic cancer cell proliferation and tumorigenicity. |
| title_sort | downregulation of traf2 mediates nik induced pancreatic cancer cell proliferation and tumorigenicity |
| url | http://europepmc.org/articles/PMC3536768?pdf=render |
| work_keys_str_mv | AT heikedoppler downregulationoftraf2mediatesnikinducedpancreaticcancercellproliferationandtumorigenicity AT geouyarhliou downregulationoftraf2mediatesnikinducedpancreaticcancercellproliferationandtumorigenicity AT peterstorz downregulationoftraf2mediatesnikinducedpancreaticcancercellproliferationandtumorigenicity |