Zhong Lou, Cao Fei, You Qingsheng
Department of Thoracic Surgery, Affiliated Hospital of Nantong University, 20 Xishi Road, Nantong, 226001, Jiangsu Province, People's Republic of China.
Tumour Biol. 2013 Feb;34(1):231-9. doi: 10.1007/s13277-012-0543-8. Epub 2012 Oct 4.
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a unique adaptor protein of the tumor necrosis factor receptor-associated factor family that mediates both tumor necrosis factor receptor and interleukin-1 receptor/Toll-like receptor signaling. A recent study showed that TRAF6 played an important role in tumorigenesis and invasion through activation of nuclear factor kappa B (NF-κB). However, the biological role of TRAF6 remains unknown in lung cancer up to now. To address the expression of TRAF6 in lung cancer cells, four lung cancer cell lines (A549, HCC827, NCI-H292, and 95-D) and human bronchial epithelial cells were used to detect the expression of TRAF6 protein by western blotting. Results indicated that TRAF6 displayed an upregulation in human lung cancer cell lines. To investigate the effects of TRAF6 on the biological behavior of human lung adenocarcinoma cell, we generated human lung adenocarcinoma A549 cell line in which TRAF6 was depleted. The results showed that downregulation of TRAF6 could decrease cell viability, suppress cell proliferation and invasion, and promote cell apoptosis. At the same time, we explored the effects of TRAF6 on the expression of the following proteins: phosphor-NF-κB (p-p65), cyclin D1, caspase-3, and matrix metalloproteinase 9 (MMP9). Downregulation of TRAF6 could decrease the expression of p-p65, cyclin D1, and MMP9 and increase the expression of caspase-3. All these results suggested that TRAF6 might be involved in the potentiation of growth, proliferation, and invasion of A549 cell line, as well as the inhibition of A549 cell apoptosis by the activation of NF-κB. To make a long story short, the overexpression of TRAF6 might be related to the tumorigenesis and invasion of lung cancer.
肿瘤坏死因子受体相关因子6（TRAF6）是肿瘤坏死因子受体相关因子家族中一种独特的衔接蛋白，介导肿瘤坏死因子受体以及白细胞介素-1受体/Toll样受体信号传导。最近一项研究表明，TRAF6通过激活核因子κB（NF-κB）在肿瘤发生和侵袭中发挥重要作用。然而，截至目前TRAF6在肺癌中的生物学作用仍不清楚。为了研究TRAF6在肺癌细胞中的表达情况，我们使用了四种肺癌细胞系（A549、HCC827、NCI-H292和95-D）以及人支气管上皮细胞，通过蛋白质免疫印迹法检测TRAF6蛋白的表达。结果表明，TRAF6在人肺癌细胞系中呈上调表达。为了研究TRAF6对人肺腺癌细胞生物学行为的影响，我们构建了TRAF6缺失的人肺腺癌A549细胞系。结果显示，TRAF6的下调可降低细胞活力，抑制细胞增殖和侵袭，并促进细胞凋亡。同时，我们探究了TRAF6对以下蛋白表达的影响：磷酸化核因子κB（p-p65）、细胞周期蛋白D1、半胱天冬酶-3和基质金属蛋白酶9（MMP9）。TRAF6的下调可降低p-p65、细胞周期蛋白D1和MMP9的表达，并增加半胱天冬酶-3的表达。所有这些结果表明，TRAF6可能通过激活NF-κB参与增强A549细胞系的生长、增殖和侵袭能力，以及抑制A549细胞凋亡。简而言之，TRAF6的过表达可能与肺癌的发生和侵袭有关。
