NIK is involved in constitutive activation of the alternative NF-κB pathway and proliferation of pancreatic cancer cells
NIK is involved in constitutive activation of the alternative NF-κB pathway and proliferation of pancreatic cancer cells
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DOI：
10.1016/j.bbrc.2009.07.125
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发表时间：
2009-10-09
影响因子：
3.1
通讯作者：
Inoue, Jun-ichiro
中科院分区：
文献类型：
--
作者：
Nishina, Takashi;Yamaguchi, Noritaka;Inoue, Jun-ichiro
胰腺癌是人类肿瘤中预后最差的肿瘤之一。在胰腺癌细胞中经常观察到核因子-kappaB的结构性激活，并与其恶性程度有关。然而，对于这种结构性的核因子-kappaB激活的分子机制却知之甚少。在这里，我们发现替代途径是结构性激活的，并且替代途径的介体--核因子-kappaB诱导激酶(NIK)在胰腺癌细胞中显著表达。SiRNA介导的Nik表达沉默和亚细胞分裂显示Nik在胰腺癌细胞中参与P100的加工和P52和RelB的核转运。此外，Nik沉默显著抑制了胰腺癌细胞的增殖。这些结果清楚地表明，NIK参与了替代途径的结构性激活，并控制了胰腺癌细胞的增殖。因此，NIK可能成为治疗胰腺癌的新靶点。(C)2009 Elsevier Inc.保留所有权利。
Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-kappa B is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-kappa B activation. Here, we show that the alternative pathway is constitutively activated and NF-kappa B-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer. (C) 2009 Elsevier Inc. All rights reserved.