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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/21847

Title: Epithelial-mesenchymal transition during invasion of cutaneous squamous cell carcinoma is paralleled by AKT activation
Authors: Barrette, K.
Van Kelst, S.
Wouters, J.
Marasigan, V.
Fieuws, S.
Agostinis, P.
van den Oord, J.
Garmyn, M.
Issue Date: 2014
Citation: BRITISH JOURNAL OF DERMATOLOGY, 171 (5), p. 1014-1021
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.
Notes: [Barrette, K.; Van Kelst, S.; Marasigan, V.; Garmyn, M.] Katholieke Univ Leuven, Dermatol Lab, Dept Oncol, Leuven, Belgium. [Wouters, J.; van den Oord, J.] Katholieke Univ Leuven, Translat Cell & Tissue Res, Dept Imaging & Pathol, Leuven, Belgium. [Fieuws, S.] Katholieke Univ Leuven, I Biostat, Interuniv Inst Biostat & Stat Bioinformat, Leuven, Belgium. [Fieuws, S.] Univ Hasselt, Leuven, Belgium. [Agostinis, P.] Katholieke Univ Leuven, Lab Cell Death Res & Therapy, Dept Cellular & Mol Med, Leuven, Belgium.
URI: http://hdl.handle.net/1942/21847
DOI: 10.1111/bjd.12967
ISI #: 000209627400020
ISSN: 0007-0963
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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