Increased FoxM1 expression is a target for metformin in the suppression of EMT in prostate cancer
Forkhead box M1 (FoxM1) transcription factor is related to the pathogenesis of various malignancies and recent evidence indicates that FoxM1 promotes epithelial-mesenchymal transition (EMT) in breast cancer. Metformin can inhibit the progression of cancer. However, whether FoxM1
plays a role in EMT in prostate cancer (PCa) and whether metformin can suppress EMT through FoxM1 in PCa remain unresolved issues. In this study, we investigated the expression levels of the FoxM1 protein in 62 PCa and 39 benign prostate hyperplasia (BPH) samples and found
that the expression levels of FoxM1 were higher in the PCa tissues (66.1%) compared with the BPH tissues (28.2%) (p<0.05). We observed that FoxM1 was expressed in the PCa cell lines and that metformin suppressed cell proliferation and the expression of FoxM1. We induced EMT in
the PCa cells by the addition of transforming growth factor (TGF)-β1 and verified the process by examining EMT-related gene (E-cadherin, vimentin and Slug) expression. In addition, the knockdown of FoxM1 by shRNA in the PCa cells reversed EMT and markedly reduced cell migration. These
results indicate that metformin suppresses EMT by inhibiting FoxM1. We demonstrate that the suppression of FoxM1 may be an effective therapeutic strategy for PCa and provide further evidence of the anticancer effects of metformin.
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Document Type: Research Article
Department of Ultrasound, Chinese PLA General Hospital, Beijing 100853, P.R. China
Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China
Department of Stomatology, Chinese PLA General Hospital, Beijing 100853, P.R. China
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China
Publication date: June 1, 2014
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The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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