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| Status |
Public on Jan 16, 2023 |
| Title |
ASPSCR1-TFE3 orchestrates the angiogenic program of alveolar soft part sarcoma [ChIP-seq] |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Alveolar soft part sarcoma (ASPS) is a rare soft part malignancy affecting adolescents and young adult. ASPS is characterized by its alveolar structure consisting of tumor cells and highly integrated vascular network, and its high metastatic potential indicates the importance of the prominent angiogenic activity of ASPS. Here we find that the expression of ASPSCR1-TFE3, the fusion transcription factor causatively associated with ASPS, is dispensable for in vitro tumor maintenance but required for in vivo tumor development via angiogenesis. ASPSCR1-TFE3 frequently associates with active enhancers including super-enhancers (SE) upon its DNA binding, and the loss of its expression induces dynamic modification of SE distribution related to genes belonging to the angiogenesis pathway. Using epigenomic CRISPR/dCas9 screening, we identify Pdgfb, Rab27a, Sytl2, and Vwf as critical target genes associated with reduced enhancer activities due to the ASPSCR1-TFE3 loss. ASPSCR1-TFE3 thus orchestrates higher ordered angiogenesis via enhanced intracellular trafficking of angiogenic factors.
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| Overall design |
Mouse ASPS was induced by expressing ASPSCR1-TFE3 in embryonic mesenchymal cells followed by subcutaneous transplantation into nude mice. Subcutaneous tumors were subjected to cell culture. Human ASPS cell lines were used for gene knockdown experiments.
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| Contributor(s) |
Tanaka M, Nakamura T |
| Citation(s) |
37029109 |
| |
| Submission date |
Nov 19, 2021 |
| Last update date |
Apr 18, 2023 |
| Contact name |
Takuro Nakamura |
| E-mail(s) |
takuro-ind@umin.net
|
| Phone |
81-3-3570-0462
|
| Organization name |
Japanese Foundation for Cancer Research
|
| Department |
The Cancer Institute
|
| Lab |
Carcinogenesis
|
| Street address |
3-8-31 Ariake, Koto-ku
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| City |
Tokyo |
| ZIP/Postal code |
135-8550 |
| Country |
Japan |
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| Platforms (4)
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| GPL15520 |
Illumina MiSeq (Homo sapiens) |
| GPL16417 |
Illumina MiSeq (Mus musculus) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (31)
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| Relations |
| SRA |
SRP346893 |
| BioProject |
PRJNA781824 |
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