Document Detail

Tetraspanin CD63 acts as a pro-metastatic factor via β-catenin stabilization.
MedLine Citation:
PMID:  25354204     Owner:  NLM     Status:  Publisher    
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. © 2014 Wiley Periodicals, Inc.
Bastian Seubert; Haissi Cui; Nicole Simonavicius; Katja Honert; Sandra Schäfer; Ute Reuning; Mathias Heikenwalder; Bernard Mari; Achim Krüger
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-29
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  -     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-29     Completed Date:  -     Revised Date:  2014-10-30    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 UICC.
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