Overexpression of FOXM1 is associated with EMT and is a predictor of poor prognosis in non-small cell lung cancer.
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 FOXM1-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/p70S6K 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/p70S6K pathway. Therefore, we suggest that FOXM1 may be a potential target for lung cancer therapy.
Department of Oncology, No. 3 People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine (SJTU-SM), Shanghai 201900, P.R. China.
Fei-Fei
FF
Kong
Department of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P.R. China.
Zeng-Qiang
ZQ
Qu
Department of Oncology, No. 3 People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine (SJTU-SM), Shanghai 201900, P.R. China.
Hai-Hua
HH
Yuan
Department of Oncology, No. 3 People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine (SJTU-SM), Shanghai 201900, P.R. China.
Jiong-Yi
JY
Wang
Department of Oncology, No. 3 People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine (SJTU-SM), Shanghai 201900, P.R. China.
Mei
M
Zhao
Department of Oncology, No. 3 People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine (SJTU-SM), Shanghai 201900, P.R. China.
Yue-Hui
YH
Guo
Department of Oncology, No. 3 People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine (SJTU-SM), Shanghai 201900, P.R. China.
Jing
J
Shi
Department of Oncology, No. 3 People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine (SJTU-SM), Shanghai 201900, P.R. China.
Xiao-Di
XD
Gong
Department of General Surgery, No. 3 People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine (SJTU-SM), Shanghai 201900, P.R. China.
You-Long
YL
Zhu
Department of Oncology, No. 3 People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine (SJTU-SM), Shanghai 201900, P.R. China.
Feng
F
Liu
Department of Oncology, No. 3 People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine (SJTU-SM), Shanghai 201900, P.R. China.
Wen-Ying
WY
Zhang
Department of Oncology, No. 3 People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine (SJTU-SM), Shanghai 201900, P.R. China.
Bin
B
Jiang
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D051058:Oncogene Protein v-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa