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| Status |
Public on Sep 20, 2013 |
| Title |
A mechanistic study on the metastasis inducing function of FUS-CHOP fusion protein in liposarcoma |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Identification of differential gene regulation pattern in human liposarcoma
The FUS-CHOP fusion protein has been found to be instrumental for specific oncogenic processes in liposarcoma, but its ability to induce metastasis and the underlying mechanisms by which this can be achieved remain unknown. In order to dissect its functional role in this context, we stably overexpressed this protein in SW872 liposarcoma and HT1080 fibrosarcoma cell lines, and were able to demonstrate that forced expression of FUS-CHOP significantly increases migration and invasion, as well as enhance lung and liver metastasis in the in vivo chicken chorioallantoic membrane (CAM) model, that is proliferation independent. Additionally, FUS-CHOP enhances the expression of matrix-metalloproteinases -2 and -9, and transactivates their promoters in vitro. Mutational analysis showed that C/EBP-β- (-769/-755), NF-κB (-525/-516) and CREB/AP-1 (-218/-207) sites were important for MMP-2, and NF-κB (-604/-598), AP-1 (-539/-532) and AP-1 (-81/-72) for MMP-9 transactivation. Moreover, a direct in vivo interaction of FUS-CHOP was observed in case of the MMP-2 promoter within region (-769/-207). siRNA data revealed that MMP-2 expression is essential in the FUS-CHOP induced metastatic phenotype. MMP-2-mRNA and protein expression correlated significantly with FUS-CHOP positivity in 31 resected patient liposarcoma tissues. We have for the first time provided substantial evidence for the FUS-CHOP oncoprotein as an inducer of metastasis that is due to the transcriptional induction of specific tumor-associated proteases. Insights gained from this study not only support a deeper understanding of the mechanistic properties of FUS-CHOP, but also open up new avenues for targeted therapy.
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| Overall design |
3 liposarcoma tumor samples, 3 corresponding normal samples, one sample replicated
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| Contributor(s) |
Patil N, Heil O |
| Citation(s) |
24285420 |
| Submission date |
Sep 20, 2013 |
| Last update date |
Feb 18, 2019 |
| Contact name |
Nitin Patil |
| E-mail(s) |
n.patil@dkfz.de
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| Organization name |
German Cancer Research Centre (DKFZ)
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| Department |
Molecular Oncology of Solid Tumors
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| Lab |
G360
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| Street address |
Im Neuenheimer Feld 280
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| City |
Heidelberg |
| State/province |
BW |
| ZIP/Postal code |
69120 |
| Country |
Germany |
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| Platforms (1) |
| GPL6884 |
Illumina HumanWG-6 v3.0 expression beadchip |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA219749 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE51049_RAW.tar |
6.3 Mb |
(http)(custom) |
TAR |
| GSE51049_non-normalized_data.txt.gz |
3.7 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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