Targeting FoxM1 inhibits proliferation, invasion and migration of nasopharyngeal carcinoma through the epithelial‑to-mesenchymal transition pathway.
High expression levels of the forkhead box M1 (FoxM1) transcription factor are associated with metastasis and poor prognosis of malignancies. However, little is known concerning its function in nasopharyngeal carcinoma (NPC). The present study aimed to investigate the impact of FoxM1 inhibition on the migration and invasion of NPC cells and the potential mechanisms. The effects of FoxM1 inhibitor treatment and FoxM1 silencing on the proliferation, migration and invasion of NPC CNE-1 and CNE-2 cells were examined by CCK-8, Transwell migration/invasion and colony formation assays. The effects of stable FoxM1 silencing on the growth and lung metastasis of implanted NPC were evaluated. The relative levels of FoxM1, zinc finger E-box binding homeobox 2 (ZEB2), Snail2 and E-cadherin in the different groups of NPC cells and tumors were determined by quantitative real-time PCR, western blotting and immunohistochemical assays. Treatment with thiostrepton, FoxM1 inhibitor, significantly reduced the survival of NPC cells. Treatment with thiostrepton and/or knockdown of FoxM1 inhibited the anchorage-independent proliferation, migration and invasion of NPC cells. Inhibition of FoxM1 also increased the relative levels of E-cadherin, but reduced ZEB2 and Snail2 expression in NPC cells. Stable FoxM1 silencing inhibited the growth and lung metastasis of implanted NPC in vivo, which was associated with increased levels of E-cadherin, but decreased ZEB2 and Snail2 expression in the NPC tumors. In conclusion, our data clearly indicate that knockdown of FoxM1 inhibited the growth and metastasis of human NPC by modulating epithelial-to-mesenchymal transition (EMT), and FoxM1 may be a potential target for the intervention of NPC.
Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
Chao
C
Yu
Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
Lili
L
Chen
Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
Lin
L
Yie
Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
Lei
L
Wei
Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
Taoyu
T
Wen
Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
Yanan
Y
Liu
Department of Otolaryngology Head and Neck Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, P.R. China.
Hongyan
H
Chen
D000818:Animals; D015820:Cadherins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics*; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics*; D020868:Gene Silencing; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000378:metabolism*; D012097:Repressor Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D013883:Thiostrepton / Q000494:pharmacology; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D000074165:Zinc Finger E-box Binding Homeobox 2
D015820:Cadherins; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; C000604407:SNAI1 protein, human; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D013883:Thiostrepton