title: FOXM1 promotes tumor cell invasion and correlates with poor prognosis in early-stage cervical cancer.
abstract: OBJECTIVE
  The forkhead box M1 (FOXM1) transcription factor plays crucial roles in regulating the proliferation, differentiation, and transformation of cells. Overexpression of FOXM1 is associated with a variety of aggressive solid carcinomas, including cervical cancer. However, the precise role and molecular mechanism responsible for the aggressive action of FOXM1 in cervical cancer remain unclear. This study investigated the cellular and molecular aggressive function of FOXM1 in cervical cancer.
  
  
  METHODS
  The FOXM1 gene and protein expression profiles were determined by quantitative polymerase chain reaction, Western blotting and immunohistochemical staining, and other cellular and molecular approaches including gene transfection, short hairpin RNA interference (RNAi), and wound-healing, migration, and invasion assays.
  
  
  RESULTS
  FOXM1 expression was significantly up-regulated at both mRNA and protein levels in early-stage cervical cancer, compared to cervical intraepithelial neoplasia and normal cervical tissues. High levels of FOXM1 expression were significantly associated with aggression in cervical cancer, and were an independent prognostic factor for poor survival in early-stage cervical cancer patients. Moreover, enforced expression of FOXM1 increased migration and invasion of cancer cells, whereas RNAi-mediated knockdown of FOXM1 had the opposite effect. In addition, up-regulation of FOXM1 increased the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in vitro and in vivo, and activated the Akt/glycogen synthase kinase-3β/Snail pathway, resulting in the promotion of migration and invasion of cervical cancer cells.
  
  
  CONCLUSIONS
  These results suggest that FOXM1 up-regulation is associated with poor prognosis in early-stage cervical cancer, and therefore it may act as a prognostic marker and a new potential target for cervical cancer treatment.
authors.affiliation: Department of Obstetrics and Gynecology, the First Affiliated Hospital, Sun Yat-sen University, Zhongshan Second Road 58, Guangzhou 510700, PR China. hsy5g777@sina.com
authors.forename: Shan-yang
authors.initials: SY
authors.lastname: He
authors.forename: Hong-wei
authors.initials: HW
authors.lastname: Shen
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Xiao-hui
authors.initials: XH
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Yuan
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.forename: Ze-Shan
authors.initials: ZS
authors.lastname: You
authors.forename: Shu-zhong
authors.initials: SZ
authors.lastname: Yao
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D051379:Mice; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology*
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9