title: Protein kinase D2 contributes to TNF-α-induced epithelial mesenchymal transition and invasion via the PI3K/GSK-3β/β-catenin pathway in hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Liver Tumor Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: YaBin
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Liver Tumor Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: JinZhang
authors.initials: J
authors.lastname: Chen
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: FengSheng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: RongCheng
authors.initials: R
authors.lastname: Luo
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Guangzhou, Guangdong, China.
authors.forename: AiMin
authors.initials: A
authors.lastname: Li
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D058534:Class I Phosphatidylinositol 3-Kinases; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000091283:Protein Kinase D2; D011494:Protein Kinases; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D038362:Glycogen Synthase Kinase 3; D019869:Phosphatidylinositol 3-Kinases; D000091283:Protein Kinase D2; D011494:Protein Kinases; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin; C484760:PIK3CA protein, human
keywords: PI3K; epithelial mesenchymal transition; hepatocellular carcinoma; protein kinase D2; β-catenin