title: Overexpression of FOXM1 is associated with metastases of nasopharyngeal carcinoma.
abstract: BACKGROUND
  The forkhead box M1 (FOXM1) transcription factor plays an important role in the metastases of many cancers. Down-regulation of FOXM1 by its inhibitor, thiostrepton, can inhibit the metastatic potential of some cancers; however, there are few studies regarding the functional signiﬁcance of FOXM1 and thiostrepton in the metastases of nasopharyngeal carcinoma (NPC) and the underlying mechanism.
  
  
  METHODS
  Expression of FOXM1 in NPC, normal nasopharyngeal tissues, a NPC cell line (C666-1), and a nasopharyngeal epithelial cell line (NP69) was investigated by immunohistochemical staining, qRT-PCR, and Western blot. The correlation between FOXM1 expression and the clinical characteristics of patients was analyzed. Moreover, the effects of thiostrepton on expression of FOXM1 in C666-1 and NP69 cells, and the invasion and migration ability of C666-1 cells were examined. The expressions of MMP-2, MMP-9, fascin-1, ezrin, and paxillin were determined after treatment with thiostrepton.
  
  
  RESULTS
  FOXM1 was overexpressed in NPC and C666-1 cells compared with normal nasopharyngeal tissues and NP69 cells. Overexpression of FOXM1 was associated with lymph node metastasis and advanced tumor stage. Moreover, thiostrepton inhibited expression of FOXM1 in C666-1 cells in a dose-dependent manner, but had a minimal effect on NP69 cells. Thiostrepton inhibited the migration and invasion ability of C666-1 cells by down-regulating the expression of MMP-2, MMP-9, fascin-1, and paxillin.
  
  
  CONCLUSIONS
  Overexpression of FOXM1 is associated with metastases of NPC patients. Thiostrepton inhibits the metastatic ability of NPC cells by down-regulating the expression of FOXM1, MMP-2, MMP-9, fascin-1, and paxillin.
authors.affiliation: Department of Otolaryngology, The First Affiliated Hospital of Chongqing Medical University , 1 Youyi Road, 400016 Chongqing , P.R. China.
authors.forename: Lizhu
authors.initials: L
authors.lastname: Jiang
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Hongyan
authors.initials: H
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D002277:Carcinoma; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology*; D051419:Paxillin / Q000378:metabolism; D013883:Thiostrepton / Q000737:chemistry; D000099149:Ezrin
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008840:Microfilament Proteins; D051419:Paxillin; D013883:Thiostrepton; D000099149:Ezrin; C107585:FOXM1 protein, human; C502658:FSCN1 protein, human; C496061:PXN protein, human; C522361:MMP2 protein, human; C579270:MMP9 protein, human
keywords: Forkhead box M1 transcription factor (FOXM1); metastases; nasopharyngeal carcinoma; oncogene; thiostrepton