Succinate Dehydrogenase 5 (SDH5) Regulates Glycogen Synthase Kinase 3β-β-Catenin-mediated Lung Cancer Metastasis

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.Background: SDH5 is in tumors. However, the functional role of SDH5 in lung cancer remains unknown.Results: SDH5 expression regulates EMT.Conclusion: SDH5 functions as a critical protein in the regulation of EMT by modulating the GSK-3β-β-catenin signaling pathway.Significance: SDH5 may be a prognostic biomarker and potential therapeutic target for lung cancer metastasis. 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. Background: SDH5 is in tumors. However, the functional role of SDH5 in lung cancer remains unknown. Results: SDH5 expression regulates EMT. Conclusion: SDH5 functions as a critical protein in the regulation of EMT by modulating the GSK-3β-β-catenin signaling pathway. Significance: SDH5 may be a prognostic biomarker and potential therapeutic target for lung cancer metastasis.