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GEO help: Mouse over screen elements for information. |
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Status |
Public on Jan 23, 2015 |
Title |
Tetraspanin CD63 acts as a pro-metastatic factor via β-catenin stabilization |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
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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Overall design |
Stable knock down of CD63 was performed in SKOV3ipL ovarian carcinoma cell line using 2 shRNAs lentiviral constructs (sh49 and sh51), and as a negative control, a shNT construct. Parental cells, control shNT and the 2 shCD63 cell lines were seeded 24 hours prior to RNA isolation on a 10 cm dish, labelling and hybridization on microarrays. One color experiment with 2 biological replicates of the 4 experimental conditions: SKOV3ipL, SKOV3ipL_shNT, SKOV3ipL_sh49 and SKOV3ipL_sh51.
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Contributor(s) |
Krüger A, Mari B, Lebrigand K, Barbry P |
Citation(s) |
25354204 |
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Submission date |
Oct 01, 2014 |
Last update date |
Jan 09, 2018 |
Contact name |
Kevin Lebrigand |
Organization name |
IPMC/CNRS
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Lab |
Functional Genomics Platform of Nice-Sophia-Antipolis, France.
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Street address |
660 route des lucioles
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City |
Valbonne - Sophia-Antipolis |
ZIP/Postal code |
06560 |
Country |
France |
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Platforms (1) |
GPL17077 |
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version) |
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Samples (8)
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Relations |
BioProject |
PRJNA262812 |
Supplementary file |
Size |
Download |
File type/resource |
GSE61957_RAW.tar |
99.8 Mb |
(http)(custom) |
TAR (of TXT) |
Processed data included within Sample table |
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