Overexpression of NF-κB inducing kinase underlies constitutive NF-κB activation in lung cancer cells
Overexpression of NF-κB inducing kinase underlies constitutive NF-κB activation in lung cancer cells
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DOI：
10.1016/j.lungcan.2010.03.001
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发表时间：
2010-12-01
期刊：
影响因子：
5.3
通讯作者：
Yamaoka, Shoji
中科院分区：
文献类型：
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作者：
Saitoh, Yasunori;Bruyn, Vicente Javier Martinez;Yamaoka, Shoji
本研究探讨NF-κ B诱导激酶（NIK）在肺癌细胞NF-κ B组成性激活中的作用。大量证据表明，NF-κ B B在人类癌细胞中经常被组成性激活，包括非小细胞肺癌组织标本和细胞系，这可能导致凋亡失调和肿瘤细胞对化疗的抵抗力增强。然而，在肺癌细胞中NF-κ B活化的机制在很大程度上仍然未知。我们在此报道了NF-κ B B诱导激酶（NIK）在非小细胞肺癌（NSCLC）细胞系中在翻译前水平的异常表达。通过RNA干扰去除NIK显著降低核NF-κ B DNA结合活性和报告基因表达。NIK缺失可诱导A549细胞凋亡，降低基质金属蛋白酶9（MMP-9）和生存素mRNA表达，影响H1299细胞的贴壁非依赖性生长，提示NIK在肿瘤表型中的作用。这些结果表明NIK在NSCLC细胞中的组成性NF-κ B活化中起关键作用，并暗示NIK作为肺癌治疗的分子靶点。(C)2010爱思唯尔爱尔兰有限公司版权所有。
The present study investigates roles for NF-kappa B inducing kinase (NIK) in constitutive NF-kappa B activation in lung cancer cells. A wealth of evidence showed that NF-kappa B is often constitutively activated in human cancer cells, including non-small cell lung cancer tissue specimens and cell lines, which may lead to deregulated apoptosis and enhanced resistance of tumor cells to chemotherapy. However, the mechanisms of NF-kappa B activation in lung cancer cells remain largely unknown. We report here that NF-kappa B inducing kinase (NIK) is aberrantly expressed at the pre-translational level in non-small cell lung cancer (NSCLC) cell lines. Depletion of NIK by RNA interference remarkably diminished nuclear NF-kappa B DNA binding activity and reporter gene expression. NIK depletion induced apoptosis in A549 cells, reduced the matrix metalloproteinase 9 (MMP-9) and survivin mRNA expression and affected efficiency of anchorage-independent H1299 cell growth, suggesting a role for NIK in the manifestation of oncogenic phenotype. These results indicate that NIK plays a key role in constitutive NF-kappa B activation in NSCLC cells and implicate NIK as a molecular target for lung cancer therapy. (C) 2010 Elsevier Ireland Ltd. All rights reserved.