Protein kinase D2 contributes to TNF-alpha-induced epithelial mesenchymal transition and invasion via the PI3K/GSK-3 beta/beta-catenin pathway in hepatocellular carcinoma
Protein kinase D2 contributes to TNF-alpha-induced epithelial mesenchymal transition and invasion via the PI3K/GSK-3 beta/beta-catenin pathway in hepatocellular carcinoma
复制标题
蛋白激酶 D2 通过 PI3K/GSK-3 β/β-catenin 通路促进肝细胞癌中 TNF-α 诱导的上皮间质转化和侵袭
作者：
Zhu Yun;Cheng Yang;Guo YaBin;Chen JinZhang;Chen FengSheng;Luo RongCheng;Li AiMin
虽然蛋白激酶D（PKD）已被证明有助于几种类型的癌症的侵袭和转移，但PKD在肝细胞癌（HCC）的上皮间质转化（EMT）中的作用仍不清楚。我们发现PKD 2在HCC中表达上调，并与HCC的转移有关。PKD 2正调控TNF-α诱导的EMT和HCC转移。机制研究表明TNF-α诱导的PKD 2活化是通过TNFR 1/TRAF 2复合物的形成介导的。PKD 2与PI 3 K的p110α和p85亚基直接结合，促进PI 3 K/Akt/GSK-3β信号级联反应，刺激EMT。总之，我们的研究结果揭示了EMT调控的新作用，并表明抑制PKD 2作为HCC的潜在治疗策略。
Although protein kinase D (PKD) has been shown to contribute to invasion and metastasis in several types of cancer, the role of PKD in the epithelial mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) has remained unclear. We found that PKD2 is up-regulated in HCC and is correlated with the metastasis of HCC. PKD2 positively regulated TNF-α-induced EMT and metastasis of HCC. Mechanistic studies revealed TNF-α-induced PKD2 activation is mediated by the formation of a TNFR1/TRAF2 complex. PKD2 bound directly to the p110α and p85 subunits of PI3K and promoted the PI3K/Akt/GSK-3β signaling cascade to stimulate EMT. In conclusion, our results have uncovered a novel role for the regulation of EMT and suggest inhibition of PKD2 as a potential therapeutic strategy for HCC.