Abstract:
: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. 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 enhances 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 46 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.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Patil N,Ahmed Kabeer Rasheed S,Abba M,Hendrik Leupold J,Schwarzbach M,Allgayer Hdoi
10.1002/ijc.28638subject
Has Abstractpub_date
2014-06-15 00:00:00pages
2808-19issue
12eissn
0020-7136issn
1097-0215journal_volume
134pub_type
杂志文章abstract::Epidermodysplasia verruciformis (EV) is considered as a model of genetic cancer due to unusual susceptibility to EV-specific human papillomaviruses (HPVs). We established an in vivo experimental system for long-term propagation of EV tissue which should facilitate the study of tumor progression in EV. Skin fragments f...
journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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abstract::Numbers of B, T and total lymphocytes, monocytes, heterophils, eosinophils and basophils have been examined in the peripheral blood of chickens between 2 and 42 days after infection with Marek's disease virus. During the stage of the acute restrictively productive virus infection of lymphoid tissues at 2-9 days after ...
journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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更新日期:1996-09-17 00:00:00
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journal_title:International journal of cancer
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abstract::The human surface antigen CD24 is over-expressed in small-cell lung cancer. Here we describe the isolation, sequencing and functional characterization of the 5'-flanking region of the human CD24 gene. A sequence (accession number: Y14692) of 3.4 kb regulates the activity of a luciferase reporter gene in CD24-expressin...
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abstract::Carcinoma of the breast is a leading hormone-dependent malignancy, resulting in a high rate of morbidity and mortality. During the complex multi-step process of tumor promotion, this common cancer is initiated as hormone-responsive (HR), non-metastatic cancer, followed by a gradual transition into a highly metastatic ...
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