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International Journal of Molecular Medicine
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Article

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
  • View Affiliations / Copyright

    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
  • Pages: 1514-1522
    |
    Published online on: March 20, 2014
       https://doi.org/10.3892/ijmm.2014.1707
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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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1 

Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar

2 

Christiansen JJ: Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 66:8319–8326. 2006. View Article : Google Scholar : PubMed/NCBI

3 

Laoukili J, Kooistra MRH, Brás A, et al: FoxM1 is required for execution of the mitotic programme and chromosome stability. Nat Cell Biol. 7:126–136. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Yang DK, Son CH, Lee SK, Choi PJ, Lee KE and Roh MS: Forkhead box M1 expression in pulmonary squamous cell carcinoma: correlation with clinicopathologic features and its prognostic significance. Hum Pathol. 40:464–470. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Kretschmer C, Sterner-Kock A, Siedentopf F, Schoenegg W, Schlag PM and Kemmner W: Identification of early molecular markers for breast cancer. Mol Cancer. 10:152011. View Article : Google Scholar : PubMed/NCBI

6 

Wang Z, Banerjee S, Kong D, Li Y and Sarkar FH: Down-regulation of Forkhead Box M1 transcription factor leads to the inhibition of invasion and angiogenesis of pancreatic cancer cells. Cancer Res. 67:8293–8300. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Kalin TV, Wang IC, Ackerson TJ, Major ML, Detrisac CJ, Kalinichenko VV, Lyubimov A and Costa RH: Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both TRAMP and LADY transgenic mice. Cancer Res. 66:1712–1720. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Sun HC, Li M, Lu JL, et al: Overexpression of Forkhead box M1 protein associates with aggressive tumor features and poor prognosis of hepatocellular carcinoma. Oncol Rep. 25:1533–1539. 2011.PubMed/NCBI

9 

Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 474:609–615. 2011. View Article : Google Scholar

10 

Green MR, Aya-Bonilla C, Gandhi MK, et al: Integrative genomic profiling reveals conserved genetic mechanisms for tumorigenesis in common entities of non-Hodgkin’s lymphoma. Genes Chromosomes Cancer. 50:313–326. 2011.PubMed/NCBI

11 

Huynh KM, Soh JW, Dash R, Sarkar D, Fisher PB and Kang D: FOXM1 expression mediates growth suppression during terminal differentiation of HO-1 human metastatic melanoma cells. J Cell Physiol. 226:194–204. 2011. View Article : Google Scholar

12 

Uddin S, Ahmed M, Hussain A, Abubaker J, Al-Sanea N, AbdulJabbar A, Ashari LH, Alhomoud S, Al-Dayel F, Jehan Z, Bavi P, Siraj AK and Al-Kuraya KS: Genome-wide expression analysis of Middle Eastern colorectal cancer reveals FOXM1 as a novel target for cancer therapy. Am J Pathol. 178:537–547. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Bektas N1, Haaf At, Veeck J, et al: Tight correlation between expression of the Forkhead transcription factor FOXMl and HER2 in human breast cancer. BMC Cancer. 8:422008. View Article : Google Scholar : PubMed/NCBI

14 

Xia L1, Mo P, Huang W, Zhang L, Wang Y, Zhu H, Tian D, Liu J, Chen Z, Zhang Y, Chen Z, Hu H, Fan D, Nie Y and Wu K: The TNF-α/ROS/HIF-1-induced upregulation of FoxMI expression promotes HCC proliferation and resistance to apoptosis. Carcinogenesis. 33:2250–2259. 2012.

15 

Wang Y1, Wen L, Zhao SH, Ai ZH, Guo JZ and Liu WC: FoxM1 expression is significantly associated with cisplatin-based chemotherapy resistance and poor prognosis in advanced non-small cell lung cancer patients. Lung Cancer. 79:173–179. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Wang IC, Chen YJ, Hughes D, et al: Forkhead box M1 regulates the transcriptional network of genes essential for mitotic progression and genes encoding the SCF (Skp2-Cks1) ubiquitin ligase. Mol Cell Biol. 25:10875–10894. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Ahmad A, Wang Z, Kong D, et al: FoxM1 down-regulation leads to inhibition of proliferation, migration and invasion of breast cancer cells through the modulation of extra-cellular matrix degrading factors. Breast Cancer Res Treat. 122:337–346. 2010. View Article : Google Scholar

18 

Priller M, Pöschl J, Abrão L, et al: Expression of FoxM1 is required for the proliferation of medulloblastoma cells and indicates worse survival of patients. Clin Cancer Res. 17:6791–6801. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Li Q, Zhang N, Jia Z, et al: Critical role and regulation of transcription factor FoxM1 in human gastric cancer angiogenesis and progression. Cancer Res. 69:3501–3509. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Karadedou CT, Gomes AR, Chen J, et al: FOXO3a represses VEGF expression through FOXM1-dependent and -independent mechanisms in breast cancer. Oncogene. 31:1845–1858. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Dai B, Kang SH, Gong W, et al: Aberrant FoxM1B expression increases matrix metalloproteinase-2 transcription and enhances the invasion of glioma cells. Oncogene. 26:6212–6219. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Balli D, Ustiyan V, Zhang Y, et al: Foxm1 transcription factor is required for lung fibrosis and epithelial-to-mesenchymal transition. EMBO J. 32:231–244. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Yang C, Chen H, Tan G, et al: FOXM1 promotes the epithelial to mesenchymal transition by stimulating the transcription of Slug in human breast cancer. Cancer Lett. 340:104–112. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Del Barco S, Vazquez-Martin A, Cufi S, et al: Metformin: multi-faceted protection against cancer. Oncotarget. 2:896–917. 2011.PubMed/NCBI

25 

Hadad SM, Hardie DG, Appleyard V and Thompson AM: Effects of metformin on breast cancer cell proliferation, the AMPK pathway and the cell cycle. Clin Transl Oncol. Dec 12–2013.(Epub ahead of print).

26 

He SY, Shen HW, Xu L, et al: FOXM1 promotes tumor cell invasion and correlates with poor prognosis in early-stage cervical cancer. Gynecol Oncol. 127:601–610. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Lu K, Yin X, Weng T, et al: Targeting WW domains linker of HECT-type ubiquitin ligase Smurf1 for activation by CKIP-1. Nat Cell Biol. 10:994–1002. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Yung MMCD, Liu VW, Yao KM and Ngan HY: Activation of AMPK inhibits cervical cancer cell growth through AKT FOXO3a FOXM1 signaling cascade. BMC Cancer. 13:3272013. View Article : Google Scholar : PubMed/NCBI

29 

Hugo H, Ackland ML, Blick T, et al: Epithelial-mesenchymal and mesenchymal-epithelial transitions in carcinoma progression. J Cell Physiol. 213:374–383. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Korver W, Roose J, Heinen K, et al: The human TRIDENT/HFH-11/FKHL16 gene: structure, localization, and promoter characterization. Genomics. 46:435–442. 1997. View Article : Google Scholar : PubMed/NCBI

31 

Laoukili J, Stahl M and Medema RH: FoxM1: at the crossroads of ageing and cancer. Biochim Biophys Acta. 1775:92–102. 2007.PubMed/NCBI

32 

Nieto MA: Epithelial-mesenchymal transitions in development and disease: old views and new perspectives. Int J Dev Biol. 53:1541–1547. 2009. View Article : Google Scholar : PubMed/NCBI

33 

Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar : PubMed/NCBI

34 

Slabáková E, Pernicová Z, Slavíčková E, Staršíchová A, Kozubík A and Souček K: TGF-β1-induced EMT of non-transformed prostate hyperplasia cells is characterized by early induction of SNAI2/Slug. Prostate. 71:1332–1343. 2011.

35 

Katsuno Y, Lamouille S and Derynck R: TGF-β signaling and epithelial-mesenchymal transition in cancer progression. Curr Opin Oncol. 25:76–84. 2013.

36 

Saitoh M and Miyazawa K: Transcriptional and post-transcriptional regulation in TGF-β-mediated epithelial-mesenchymal transition. J Biochem. 151:563–571. 2012.

37 

Lin T, Ponn A, Hu X, Law BK and Lu J: Requirement of the histone demethylase LSD1 in Snai1-mediated transcriptional repression during epithelial-mesenchymal transition. Oncogene. 29:4896–4904. 2010. View Article : Google Scholar : PubMed/NCBI

38 

Gorbachinsky I, Akpinar H and Assimos DG: Metabolic syndrome and urologic diseases. Rev Urol. 12:e157–e180. 2010.PubMed/NCBI

39 

Parsons JK, Carter HB, Partin AW, et al: Metabolic factors associated with benign prostatic hyperplasia. J Clin Endocrinol Metab. 91:2562–2568. 2006. View Article : Google Scholar : PubMed/NCBI

40 

Jalving M, Gietema JA, Lefrandt JD, et al: Metformin: taking away the candy for cancer? Eur J Cancer. 46:2369–2380. 2010. View Article : Google Scholar : PubMed/NCBI

41 

Cufi S, Vazquez-Martin A, Oliveras-Ferraros C, Martin-Castillo B, Joven J and Menendez JA: Metformin against TGFβ-induced epithelial-to-mesenchymal transition (EMT): from cancer stem cells to aging-associated fibrosis. Cell Cycle. 9:4461–4468. 2010.

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Copy and paste a formatted citation
Spandidos Publications style
Wang Y, Yao B, Wang Y, Zhang M, Fu S, Gao H, Peng R, Zhang L and Tang J: Increased FoxM1 expression is a target for metformin in the suppression of EMT in prostate cancer. Int J Mol Med 33: 1514-1522, 2014.
APA
Wang, Y., Yao, B., Wang, Y., Zhang, M., Fu, S., Gao, H. ... Tang, J. (2014). Increased FoxM1 expression is a target for metformin in the suppression of EMT in prostate cancer. International Journal of Molecular Medicine, 33, 1514-1522. https://doi.org/10.3892/ijmm.2014.1707
MLA
Wang, Y., Yao, B., Wang, Y., Zhang, M., Fu, S., Gao, H., Peng, R., Zhang, L., Tang, J."Increased FoxM1 expression is a target for metformin in the suppression of EMT in prostate cancer". International Journal of Molecular Medicine 33.6 (2014): 1514-1522.
Chicago
Wang, Y., Yao, B., Wang, Y., Zhang, M., Fu, S., Gao, H., Peng, R., Zhang, L., Tang, J."Increased FoxM1 expression is a target for metformin in the suppression of EMT in prostate cancer". International Journal of Molecular Medicine 33, no. 6 (2014): 1514-1522. https://doi.org/10.3892/ijmm.2014.1707
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Y, Yao B, Wang Y, Zhang M, Fu S, Gao H, Peng R, Zhang L and Tang J: Increased FoxM1 expression is a target for metformin in the suppression of EMT in prostate cancer. Int J Mol Med 33: 1514-1522, 2014.
APA
Wang, Y., Yao, B., Wang, Y., Zhang, M., Fu, S., Gao, H. ... Tang, J. (2014). Increased FoxM1 expression is a target for metformin in the suppression of EMT in prostate cancer. International Journal of Molecular Medicine, 33, 1514-1522. https://doi.org/10.3892/ijmm.2014.1707
MLA
Wang, Y., Yao, B., Wang, Y., Zhang, M., Fu, S., Gao, H., Peng, R., Zhang, L., Tang, J."Increased FoxM1 expression is a target for metformin in the suppression of EMT in prostate cancer". International Journal of Molecular Medicine 33.6 (2014): 1514-1522.
Chicago
Wang, Y., Yao, B., Wang, Y., Zhang, M., Fu, S., Gao, H., Peng, R., Zhang, L., Tang, J."Increased FoxM1 expression is a target for metformin in the suppression of EMT in prostate cancer". International Journal of Molecular Medicine 33, no. 6 (2014): 1514-1522. https://doi.org/10.3892/ijmm.2014.1707
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