Downregulation of TRAF2 mediates NIK-induced pancreatic cancer cell proliferation and tumorigenicity.
Downregulation of TRAF2 mediates NIK-induced pancreatic cancer cell proliferation and tumorigenicity.
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DOI：
10.1371/journal.pone.0053676
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Storz P
中科院分区：
文献类型：
--
作者：
Döppler H;Liou GY;Storz P
NF-κB水平升高是胰腺导管腺癌（PDAC）的标志，经典和替代NF-κB活化途径均涉及其中。在这里，我们表明，旁路途径的激活是PDAC细胞系中高基础NF-κB活性的来源。p52/RelB NF-κB复合物活性的增加是通过NF-κ B诱导激酶（NIK）的稳定和活化介导的。我们确定TNF受体相关因子2（TRAF 2）的蛋白酶体下调作为PDAC细胞系中活性NIK水平增加的机制。NIK表达和活性水平的这种上调与PDAC细胞的增殖和非贴壁依赖性生长增加有关，但与PDAC细胞的迁移或存活无关。快速生长是胰腺癌的特征之一。我们的数据表明TRAF 2/NIK/NF-κB2通路调节PDAC细胞的致瘤性，并可能成为治疗这种癌症的有价值的靶点。
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.
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影响因子：
30.5
作者：
通讯作者：
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影响因子：
56.9
作者：
Yang, Y;Fang, SY;Ashwell, JD
通讯作者：
Ashwell, JD
影响因子：
13
作者：
Thu, Yee Mon;Richmond, Ann
通讯作者：
Richmond, Ann
影响因子：
30.5
作者：
Zarnegar, Brian J.;Wang, Yaya;Mahoney, Douglas J.;Dempsey, Paul W.;Cheung, Herman H.;He, Jeannie;Shiba, Travis;Yang, Xiaolu;Yeh, Wen-chen;Mak, Tak W.;Korneluk, Robert G.;Cheng, Genhong
通讯作者：
Cheng, Genhong
DOI：
10.1016/j.bbrc.2009.07.125
发表时间：
2009-10-09
影响因子：
3.1
作者：
Nishina, Takashi;Yamaguchi, Noritaka;Inoue, Jun-ichiro
通讯作者：
Inoue, Jun-ichiro