Increased FoxM1 expression is a target for metformin in the suppression of EMT in prostate cancer

Wang,Yiru; Yao,Binwei; Wang,Yu; Zhang,Mingbo; Fu,Shuai; Gao,Hanjing; Peng,Ruiyun; Zhang,Lingqiang; Tang,Jie

doi:10.3892/ijmm.2014.1707

Increased FoxM1 expression is a target for metformin in the suppression of EMT in prostate cancer

Authors:
- Yiru Wang
- Binwei Yao
- Yu Wang
- Mingbo Zhang
- Shuai Fu
- Hanjing Gao
- Ruiyun Peng
- Lingqiang Zhang
- Jie Tang
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Affiliations: 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
Published online on: March 20, 2014 https://doi.org/10.3892/ijmm.2014.1707
Pages: 1514-1522

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Abstract

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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