Metformin inhibits TGF-β1-induced epithelial-to-mesenchymal transition-like process and stem-like properties in GBM via AKT/mTOR/ZEB1 pathway
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Yang Song1, Yong Chen1, Yunqian Li1, Xiaoyan Lyu2, Jiayue Cui3, Ye Cheng1, Liyan Zhao2 and Gang Zhao1
1Department of Neurosurgery, First Hospital, Jilin University, Changchun, Jilin 130021, China
2Department of Medical Laboratory, Second Hospital, Jilin University, Changchun, Jilin 130041, China
3Department of Histology and Embryology, College of Basic Medicine, Jilin University, Changchun, Jilin 130021, China
Gang Zhao, email: firstname.lastname@example.org
Liyan Zhao, email: email@example.com
Keywords: glioblastoma; metformin; epithelial-to-mesenchymal transition; glioblastoma stem cells; AKT/mTOR/ZEB1 pathway
Received: September 06, 2017 Accepted: November 19, 2017 Published: December 15, 2017
Glioblastoma (GBM) is the most frequent and aggressive brain tumor in adults. In spite of advances in diagnosis and therapy, the prognosis is still relatively poor. The invasive property of GBM is the major cause of death in patients. Epithelial-to-mesenchymal transition-like process (EMT-like process) is considered to play an important role in the invasive property. Metformin has been reported as a regulator of EMT-like process. In this study, we confirmed that metformin inhibited TGF-β1-induced EMT-like process and EMT-associated migration and invasion in LN18 and U87 GBM cells. Our results also showed that metformin significantly suppressed self-renewal capacity of glioblastoma stem cells (GSCs), and expression of stem cell markers Bmi1, Sox2 and Musashi1, indicating that metformin can inhibit cancer stem-like properties of GBM cells. We further clarified that metformin specifically inhibited TGF-β1 activated AKT, the downstream molecular mTOR and the leading transcription factor ZEB1. Taken together, our data demonstrate that metformin inhibits TGF-β1-induced EMT-like process and cancer stem-like properties in GBM cells via AKT/mTOR/ZEB1 pathway and provide evidence of metformin for further clinical investigation targeted GBM.
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