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Seubert, B.* ; Cui, H.* ; Simonavicius, N. ; Honert, K.* ; Schafer, S.* ; Reuning, U.* ; Heikenwälder, M. ; Mari, B.* ; Krüger, A.*

Tetraspanin CD63 acts as a pro-metastatic factor via β-catenin stabilization.

Int. J. Cancer 136, 2304-2315 (2015)
Verlagsversion Postprint DOI
Open Access Green
The tetraspanin CD63 is implicated in pro-metastatic signaling pathways but, so far, it is unclear, how CD63 levels affect the tumor cell phenotype. Here, we investigated the effect of CD63 modulation in different metastatic tumor cell lines. In vitro, knock down of CD63 induced a more epithelial-like phenotype concomitant with increased E-cadherin expression, downregulation of its repressors Slug and Zeb1, and decreased N-cadherin. In addition, β-catenin protein was markedly reduced, negatively affecting expression of the target genes MMP-2 and PAI-1. β-catenin inhibitors mimicked the epithelial phenotype induced by CD63 knock down. Inhibition of β-catenin upstream regulators PI3K/AKT or GSK3β could rescue the mesenchymal phenotype underlining the importance of the β-catenin pathway in CD63-regulated cell plasticity. CD63 knock down-induced phenotypical changes correlated with a decrease of experimental metastasis while CD63 overexpression enhanced the tumor cell-intrinsic metastatic potential. Taken together, our data show that CD63 is a crucial player in the regulation of the tumor cell-intrinsic metastatic potential by affecting cell plasticity.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cd63 ; Epithelial Mesenchymal Transition (emt) ; Mesenchymal To Epithelial Transition (met) ; Cancer ; Tetraspanin ; Beta-catenin ; E-cadherin ; Pi3k ; Gsk3 ; Metastasis; Epithelial-mesenchymal Transition; Human-melanoma; Tissue Inhibitor; Cell-migration; Stem-cells; Cancer; Protein; Web; Dissemination; Colonization
ISSN (print) / ISBN 0020-7136
e-ISSN 1097-0215
Quellenangaben Band: 136, Heft: 10, Seiten: 2304-2315 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Hoboken
Begutachtungsstatus Peer reviewed