Suppression of cell invasiveness by periostin via TAB1/TAK1
Suppression of cell invasiveness by periostin via TAB1/TAK1
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DOI：
10.3892/ijo_00000355
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发表时间：
2009-08-01
影响因子：
5.2
通讯作者：
Inoue, Hirokazu
中科院分区：
文献类型：
--
作者：
Isono, Takahiro;Kim, Chul Jang;Inoue, Hirokazu
我们先前已经表明，骨膜蛋白的表达在人膀胱癌组织中显著下调，并且骨膜蛋白抑制癌细胞的细胞侵袭和转移。为了阐明骨膜蛋白抑制的分子机制，我们寻找骨膜蛋白结合蛋白，并通过对表达骨膜蛋白的293 T细胞中与骨膜蛋白共沉淀的蛋白质进行质量分析，鉴定了与TAK 1相互作用并激活TAK 1的TAB 1。通过在与骨膜蛋白、TAB 1和TAK 1的表达质粒共转染的293 T细胞中的下拉测定来证实骨膜蛋白和TAB 1之间的关联。在该测定中，TAK 1也与骨膜蛋白共沉淀。在293 T中的共转染实验也表明periostin可以激活TAK 1。针对TAB 1的siRNA的引入抑制了骨膜蛋白对TAK 1的激活。对骨膜蛋白缺失突变体的分析表明，骨膜蛋白的C端区域对于与TAB 1的关联和TAK 1的激活是必要的和充分的。在293 T（人胚肾）和T24（人膀胱癌）细胞系中，通过靶向TAK 1或TAB 1的siRNA减弱骨膜蛋白对侵袭性的抑制。这些发现表明骨膜蛋白通过TAB 1/TAK 1信号通路参与抑制细胞侵袭。
We have previously shown that the expression of periostin is significantly downregulated in human bladder cancer tissues and that periostin suppresses cell invasiveness and metastasis of cancer cells. To clarify the molecular mechanism of this suppression by periostin, we searched for periostin-binding proteins and identified TAB1, which interacts with and activates TAK1, by mass analysis of proteins co-precipitated with periostin in 293T cells expressing periostin. The association between periostin and TAB1 was confirmed by a pulldown assay in 293T cells co-tranfected with expression plasmids of periostin, TAB1 and TAK1. TAK1 was also co-precipitated with periostin in this assay. Co-transfection experiments in 293T also showed that periostin could activate TAK1. Introduction of siRNA for TAB1 suppressed TAK1 activation by periostin. Analyses with deletion mutants of periostin revealed that the C-terminal region of periostin was necessary and sufficient for the association with TAB1 and the TAK1 activation. The suppression of invasiveness by periostin was attenuated by siRNA targeting TAK1 or TAB1 in 293T (human embryonic kidney) and T24 (human bladder carcinoma) cell lines. These findings indicate that periostin is involved in the suppression of cell invasiveness via the TAB1/TAK1 signaling pathway.