Protein kinase D2 contributes to TNF-α-induced epithelial mesenchymal transition and invasion via the PI3K/GSK-3β/β-catenin pathway in hepatocellular carcinoma.
机构：[1]Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong, China[2]Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China[3]Liver Tumor Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
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.
基金：
This study was supported by the National Nature Science Foundation of China (No. 81372153); Postdoctor Research Funding of Guangzhou Women and Children’s Medical Center (5001-2150172); Guangdong Nature Science Foundation (2015A030313261); Innovation Power School-Start Program of Southern Medical University (C1031846).
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外文
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出版当年[2015]版：
大类|1 区医学
小类|2 区肿瘤学3 区细胞生物学
最新[2025]版：
无
第一作者：
第一作者机构：[1]Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong, China
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推荐引用方式(GB/T 7714)：
Yun Zhu,Yang Cheng,YaBin Guo,et al.Protein kinase D2 contributes to TNF-α-induced epithelial mesenchymal transition and invasion via the PI3K/GSK-3β/β-catenin pathway in hepatocellular carcinoma.[J].Oncotarget.2016,7(5):5327-41.doi:10.18632/oncotarget.6633.
APA：
Yun Zhu,Yang Cheng,YaBin Guo,JinZhang Chen,FengSheng Chen...&AiMin Li.(2016).Protein kinase D2 contributes to TNF-α-induced epithelial mesenchymal transition and invasion via the PI3K/GSK-3β/β-catenin pathway in hepatocellular carcinoma..Oncotarget,7,(5)
MLA：
Yun Zhu,et al."Protein kinase D2 contributes to TNF-α-induced epithelial mesenchymal transition and invasion via the PI3K/GSK-3β/β-catenin pathway in hepatocellular carcinoma.".Oncotarget 7..5(2016):5327-41
医学