Discs large homolog 5 decreases formation and function of invadopodia in human hepatocellular carcinoma via Girdin and Tks5: Dlg5 regulates HCC invadopodia
文献类型：期刊论文
| 作者 | Ke Y1; Bao TH1,2; Fu BM1; Wu XS5; Tang HR5; Shi ZT1; Lei XF6; Zhang C1; Zhou QX3; Tan YQ1 |
| 刊名 | International Journal of Cancer
 |
| 出版日期 | 2017 |
| 卷号 | **期号:**页码:Epub ahead of print |
| 关键词 | Dlg5 protein Human hepatocellular carcinoma Invadopodia Key-words CCDC88A protein SH3PXD2A protein |
| 其他题名 | wanglinghjt@hotmail.com or linwang0705@126.com |
| 英文摘要 | Invadopodium formation is a crucial early event of invasion and metastasis of hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying regulation of invadopodia remain elusive. This study aimed to investigate the potential role of discs large homolog 5 (Dlg5) in invadopodium formation and function in HCC. We found that Dlg5 expression was significantly lower in human HCC tissues and cell lines than adjacent non-tumor tissues and liver cells. Lower Dlg5 expression was associated with advanced stages of HCC, and poor overall and disease-free survival of HCC patients. Dlg5-silencing promoted epithelial-mesenchymal transition, invadopodium formation, and gelatin degradation function, as well as invadopodium-associated invasion of HepG2 cells. In contrast, Dlg5 over-expression inhibited epithelial-mesenchymal transition, functional invadopodium formation, and invasion of SK-Hep1 cells. Both Girdin and Tks5, but not the Tks5 non-phosphorylatable mutant, were responsible for the enhanced invadopodium formation and invasion of Dlg5-silenced HepG2 cells. Furthermore, Dlg5 interacted with Girdin and interfered with the interaction of Girdin and Tks5. Dlg5-silencing promoted Girdin and Tks5 phosphorylation, which was abrogated by Girdin silencing and rescued by inducing shRNA-resistant Girdin expression. Moreover, Dlg5 over-expression significantly inhibited HCC intrahepatic and lung metastasis in vivo. Taken together, our data indicate that Dlg5 acts as a novel regulator of invadopodium-associated invasion via Girdin and by interfering with the interaction between Girdin and Tks5, which might be important for Tks5 phosphorylation in HCC cells. Conceivably, Dlg5 may act as a new biomarker for prognosis of HCC patients. This article is protected by copyright. All rights reserved. |
| 收录类别 | SCI |
| 资助信息 | The authors would like to express their sincere gratitude to Prof. Lin Xu (Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, CAS) and his group for helpful scientific discussions and technical support |
| 语种 | 英语 |
| 源URL | [http://159.226.149.26:8080/handle/152453/11040]  |
| 专题 | 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 昆明动物研究所_学习记忆的分子神经机制 |
| 作者单位 | 1.Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, China 2.the Mental Health Center of Kunming Medical University, Kunming, China 3.Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China 4.Department of Pathology, the Second Affiliated Hospital of Kunming Medical University, Kunming, China 5.Department of Gastroenterological Surgery, the Second Affiliated Hospital of Kunming Medical University, Kunming, China 6.Deparment of Medical Oncology, the Second Affiliated Hospital of Kunming Medical University, Kunming, China |
| 推荐引用方式 GB/T 7714 | Ke Y,Bao TH,Fu BM,et al. Discs large homolog 5 decreases formation and function of invadopodia in human hepatocellular carcinoma via Girdin and Tks5: Dlg5 regulates HCC invadopodia[J]. International Journal of Cancer,2017,**(**):Epub ahead of print. |
| APA | Ke Y.,Bao TH.,Fu BM.,Wu XS.,Tang HR.,...&Ge JY.(2017).Discs large homolog 5 decreases formation and function of invadopodia in human hepatocellular carcinoma via Girdin and Tks5: Dlg5 regulates HCC invadopodia.International Journal of Cancer,**(**),Epub ahead of print. |
| MLA | Ke Y,et al."Discs large homolog 5 decreases formation and function of invadopodia in human hepatocellular carcinoma via Girdin and Tks5: Dlg5 regulates HCC invadopodia".International Journal of Cancer **.**(2017):Epub ahead of print. |
入库方式： OAI收割
来源：昆明动物研究所
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