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Tetraspanin CD 63 acts as a pro‐metastatic factor via β‐catenin stabilization
Author(s) -
Seubert Bastian,
Cui Haissi,
Simonavicius Nicole,
Honert Katja,
Schäfer Sandra,
Reuning Ute,
Heikenwalder Mathias,
Mari Bernard,
Krüger Achim
Publication year - 2014
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29296
Subject(s) - tetraspanin , downregulation and upregulation , phenotype , cd63 , cancer research , biology , microbiology and biotechnology , pi3k/akt/mtor pathway , tumor progression , cell , signal transduction , microvesicles , gene , microrna , genetics
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 whereas 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.