期刊
ONCOLOGY REPORTS
卷 31, 期 6, 页码 2660-2668出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2014.3129
关键词
FOXM1; epithelial-mesenchymal transition; E-cadherin; Vimentin; non-small cell lung cancer; AKT
类别
资金
- Shanghai Jiaotong University School of Medicine Science Fund Project [11XJ22014]
- Hospital Foundation of No. 3 People's Hospital [syz2011-05]
- Education Fund for Outstanding Young Teachers of Shanghai [zzjdyx12111]
- Shanghai Jiaotong University School of Medicine [10JC1409200]
- Science and Technology Commission of Shanghai Municipality
Forkhead box M1 (FOXM1), a member of the Fox family of transcriptional factors, is considered to be an independent predictor of poor survival in many solid cancers. However, the underlying mechanism is not yet clear. The aim of the present study was to investigate the clinical significance of the correlation between FOXM1 and epithelial-mesenchymal transition (EMT) in non-small cell lung carcinoma and the possible mechanism responsible for FOXMl-induced EMT and metastasis. In the present study, expression levels of FOXM1 and EMT indicator proteins were determined by tissue microarray (TMA) and immunohistochemical staining, western blotting and reverse transcription-PCR (RT-PCR). Other cellular and molecular approaches including gene transfection, small interfering RNA (siRNA), and migration and invasion assays were utilized. Our results demonstrated that FOXM1 overexpression was statistically significantly associated with a higher TNM stage (p=0.036), lymph node metastasis (p=0.009) and a positive smoking history of the patients (p=0.044). Additionally, high expression of FOXM1 correlated with loss of E-cadherin expression (p<0.001) and anomalous immunopositivity of Vimentin (p=0.002). Moreover, patient survival analysis demonstrated that high expression of FOXM1 (p=0.043) and the presence of lymph node metastasis (p=0.042) were independent prognostic factors for non-small cell lung cancer (NSCLC). Furthermore, various in vitro experiments indicated that overexpression or knockdown of FOXM1 expression altered EMT through activation or inhibition of the AKT/p70(S6K) signaling pathway. Collectively, the results suggest that FOXM1 may be used as a prognostic indicator for patients with NSCLC and promotes metastasis by inducing EMT of lung cancer cells through activation of the AKT/p70(S6K) pathway. Therefore, we suggest that FOXM1 may be a potential target for lung cancer therapy.
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