Epithelial-mesenchymal transition during invasion of cutaneous squamous cell carcinoma is paralleled by AKT activation.
Br J Dermatol
; 171(5): 1014-21, 2014 Nov.
Article
en En
| MEDLINE
| ID: mdl-24628329
ABSTRACT
BACKGROUND:
Epithelial-mesenchymal transition (EMT) is required for tumour invasion and dissemination to occur.OBJECTIVES:
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
/
Carcinoma de Células Escamosas
/
Biomarcadores de Tumor
/
Proteínas Proto-Oncogénicas c-akt
/
Transición Epitelial-Mesenquimal
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Br J Dermatol
Año:
2014
Tipo del documento:
Article
País de afiliación:
Bélgica