title: Epithelial-mesenchymal transition during invasion of cutaneous squamous cell carcinoma is paralleled by AKT activation.
abstract: BACKGROUND
  Epithelial-mesenchymal transition (EMT) is required for tumour invasion and dissemination to occur.
  
  
  OBJECTIVE
  To investigate EMT during invasion of cutaneous squamous cell carcinoma (cSCC) and the involvement of AKT.
  
  
  METHODS
  Using a tissue microarray, we measured expression of EMT-markers and AKT activation in 140 samples from patients with skin cancer and matched samples of normal skin adjacent to cSCC in cSCC in situ (cSCCIS) and in invasive cSCC. We investigated EMT using functional assays and the expression of EMT markers in an isogenic skin cancer progression model using cell lines derived from dysplastic forehead skin (PM1), primary invasive cSCC (MET1) and its lymph node metastasis (MET4). This model was used to investigate AKT-specific inhibition of the EMT process.
  
  
  RESULTS
  In comparison with normal skin, and normal skin plus cSCCIS, the invasive cSCCs show significantly increased vimentin expression, decreased E-cadherin expression and increased expression of the active form of AKT. In the cell culture model, the primary MET1 cells display the lowest adhesion potential, the highest migratory and invasive ability through a Matrigel-coated porous membrane, the highest expression of EMT markers vimentin and Slug and the lowest expression of the epithelial marker E-cadherin. Pharmacological AKT inhibition in this model suppressed EMT mechanisms.
  
  
  CONCLUSIONS
  AKT may serve as a therapeutic target to avoid dissemination of cSCC cells.
authors.affiliation: Laboratory of Dermatology, Department of Oncology, KU Leuven, Leuven, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Barrette
authors.forename: S
authors.initials: S
authors.lastname: Van Kelst
authors.forename: J
authors.initials: J
authors.lastname: Wouters
authors.forename: V
authors.initials: V
authors.lastname: Marasigan
authors.forename: S
authors.initials: S
authors.lastname: Fieuws
authors.forename: P
authors.initials: P
authors.lastname: Agostinis
authors.forename: J
authors.initials: J
authors.lastname: van den Oord
authors.forename: M
authors.initials: M
authors.lastname: Garmyn
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation / Q000502:physiology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D000071250:Snail Family Transcription Factors; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology; D014746:Vimentin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin; D051057:Proto-Oncogene Proteins c-akt