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GEO help: Mouse over screen elements for information. |
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Status |
Public on Oct 29, 2012 |
Title |
Tetraspanin TSPAN12 regulates tumor growth and metastasis and inhibits β-catenin degradation |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Ablation of tetraspanin protein TSPAN12 from human MDA-MB-231 cells significantly decreased primary tumor xenograft growth, while increasing tumor apoptosis. Furthermore, TSPAN12 removal markedly enhanced tumor-endothelial interactions and increased metastasis to mouse lungs. TSPAN12 removal from human MDA-MB-231 cells also caused diminished association between FZD4 (a key canonical Wnt pathway receptor) and its co-receptor LRP5. The result likely explains substantially enhanced proteosomal degradation of β-catenin, a key effecter of canonical Wnt signalling. Consistent with disrupted canonical Wnt signaling, TSPAN12 ablation altered expression of LRP5, Naked 1 and 2, DVL2, DVL3, Axin 1 and GSKβ3 proteins. TSPAN12 ablation also altered expression of several genes regulated by β-catenin (e.g. CCNA1, CCNE2, WISP1, ID4, SFN, ME1) that may help to explain altered tumor growth and metastasis. In conclusion, these results provide the first evidence for TSPAN12 playing a role in supporting primary tumor growth and suppressing metastasis. TSPAN12 appears to function by stabilizing FZD4-LRP5 association, in support of canonical Wnt-pathway signaling, leading to enhanced β-catenin expression and function.
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Overall design |
4 samples = 2 Control + 2 TSPAN12KD
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Contributor(s) |
Knoblich K, Sharma C, Wang H, Fletcher AL, Turley SJ, Hemler ME |
Citation(s) |
23955570 |
Submission date |
Oct 28, 2012 |
Last update date |
Dec 06, 2018 |
Contact name |
Konstantin Knoblich |
Organization name |
Monash University
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Department |
Biochemistry and Molecular Biology
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Lab |
STIMMLAB
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Street address |
15 Innovation Walk
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City |
Clayton |
State/province |
VIC |
ZIP/Postal code |
3800 |
Country |
Australia |
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Platforms (1) |
GPL571 |
[HG-U133A_2] Affymetrix Human Genome U133A 2.0 Array |
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Samples (4)
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Relations |
BioProject |
PRJNA178411 |
Supplementary file |
Size |
Download |
File type/resource |
GSE41892_RAW.tar |
8.1 Mb |
(http)(custom) |
TAR (of CEL) |
GSE41892_TSPAN12KD.gct.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
Processed data included within Sample table |
Processed data are available on Series record |
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