title: TWIST1 is a molecular marker for a poor prognosis in oral cancer and represents a potential therapeutic target.
abstract: BACKGROUND
  Locoregional recurrence and distant metastases are ominous events in patients with advanced oral squamous cell carcinoma (OSCC). The objective of this study was to identify functional biomarkers that are predictive of OSCC progression to metastasis.
  
  
  METHODS
  The expression profile of a network of epithelial-mesenchymal transition (EMT) genes was investigated in a large cohort of patients with progressive OSCC using a complimentary DNA microarray platform coupled to quantitative reverse transcriptase-polymerase chain reaction and immunohistochemical analyses. Therapeutic potential was investigated in vitro and in vivo using an orthotopic mouse model of metastatic OSCC growing in the tongue microenvironment.
  
  
  RESULTS
  Among deregulated EMT genes, the Twist-related protein 1 (TWIST1) transcription factor and several of its regulated genes were significantly overexpressed across advanced stages of OSCC. This result was corroborated by the clinical observation that Twist1 up-regulation predicted the occurrence of lymph node and lung metastases as well as poor patient survival. In support of Twist1 as a driver of OSCC progression, the up-regulation of Twist1 was observed in cells isolated from patients with metastatic OSCC. The inhibition of Twist1 in these metastatic cells induced a potent inhibition of cell invasiveness in vitro as well as progression in vivo.
  
  
  CONCLUSIONS
  The current results provide evidence for the prognostic value and therapeutic potential of a network of Twist genes in patients with advanced OSCC.
authors.affiliation: Department of Head and Neck Surgery and Otorhinolaryngology, AC Camargo Cancer Center, São Paulo, Brazil; Lady Davis Institute for Medical Research and Segal Cancer Center, Jewish General Hospital, Montreal, Quebec, Canada; Department of Otolaryngology-Head and Neck Surgery, McGill University, Montreal, Quebec, Canada.
authors.forename: Sabrina Daniela
authors.initials: SD
authors.lastname: da Silva
authors.forename: Moulay A
authors.initials: MA
authors.lastname: Alaoui-Jamali
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: Soares
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro
authors.forename: Helena Paula
authors.initials: HP
authors.lastname: Brentani
authors.forename: Michael
authors.initials: M
authors.lastname: Hier
authors.forename: Silvia Regina
authors.initials: SR
authors.lastname: Rogatto
authors.forename: Luiz Paulo
authors.initials: LP
authors.lastname: Kowalski
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D051379:Mice; D009062:Mouth Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D011379:Prognosis; D051879:Twist-Related Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1
keywords: Twist; clinical outcome; epithelial-mesenchymal transition; metastasis; oral squamous cell carcinoma