1. Succinate Dehydrogenase 5 (SDH5) Regulates Glycogen Synthase Kinase 3β-β-Catenin-mediated Lung Cancer Metastasis*
- Author
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Hua Zhang, Jun Liu, Daowei Wang, Jianquan Zhu, Cong Pang, Changli Wang, Liuwei Gao, and Meng Wang
- Subjects
Male ,Beta-catenin ,Epithelial-Mesenchymal Transition ,Lung Neoplasms ,Blotting, Western ,Mice, Nude ,Vimentin ,Biochemistry ,Metastasis ,Mitochondrial Proteins ,Glycogen Synthase Kinase 3 ,Mice ,GSK-3 ,Cell Movement ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Gene Regulation ,Epithelial–mesenchymal transition ,Protein Phosphatase 2 ,Neoplasm Metastasis ,Lung cancer ,Molecular Biology ,beta Catenin ,Mice, Knockout ,Glycogen Synthase Kinase 3 beta ,Microscopy, Confocal ,biology ,Cell Biology ,respiratory system ,medicine.disease ,Immunohistochemistry ,respiratory tract diseases ,Tumor Burden ,Succinate Dehydrogenase ,Catenin ,biology.protein ,Cancer research ,Heterografts ,RNA Interference ,Signal transduction ,Protein Binding ,Signal Transduction - Abstract
We demonstrate that loss of succinate dehydrogenase 5 (SDH5) expression initiates epithelial-mesenchymal transition (EMT), which is visualized by the repression of E-cadherin and up-regulation of vimentin in lung cancer cell lines and clinical lung cancer specimens. In SDH5 knock-out mice, lung epithelial cells exhibited elevated mesenchymal markers, which is characteristic of EMT. Using a human lung xenograft-mouse model, we observed that knocking down endogenous SDH5 in human carcinoma cells leads to the development of multiple lymph node metastases. Moreover, our data indicate that SDH5 functions as a critical protein in regulating EMT by modulating the glycogen synthase kinase (GSK)-3β-β-catenin signaling pathway. These results reveal a critical role for SDH5 in EMT and suggest that SDH5 may be a prognostic biomarker and potential therapeutic target for lung cancer metastasis.
- Published
- 2013