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SATB2 induces transcriptional programs in melanoma that lead to metastatic behavior [RNA-Seq]

UID: 10779

Author(s): van Rooijen, Ellen, Yang, Song, Zhou, Yi, Zon, Leonard I.

Description
Summary from the GEO: "We report gene expression data for zebrafish melanomas overexpressing human SATB2 and EGFP."

Overall design from the GEO: "RNA-seq was performed on three biological replicates of primary zebrafish melanoma tumors that were excized from MCR:EGFP (control) and MCR:SATB2 overexpressing Tg(BRAF V600E);p53-/-; mitf-/- zebrafish."

Abstract summary: "Recent genomic and scRNA-seq analyses of melanoma demonstrated a lack of recurrent genetic drivers of metastasis, while identifying common transcriptional states correlating with invasion or drug resistance. To test whether transcriptional adaptation can drive melanoma progression, we made use of a zebrafish mitfa:BRAFV600E;tp53-/-model, in which malignant progression is characterized by minimal genetic evolution. We undertook an overexpression-screen of 80 epigenetic/transcriptional regulators and found neural crest-mesenchyme developmental regulator SATB2 to accelerate aggressive melanoma development. Its overexpression induces invadopodia formation and invasion in zebrafish tumors and human melanoma cell lines. SATB2 binds and activates neural crest-regulators, including pdgfab and snai2. The transcriptional program induced by SATB2 overlaps with known MITFlowAXLhigh and AQP1+NGFR1high drug-resistant states and functionally drives enhanced tumor propagation and resistance to Vemurafenib in vivo. In summary, we show that melanoma transcriptional rewiring by SATB2 to a neural crest mesenchyme-like program can drive invasion and drug resistance in autochthonous tumors."
Subject of Study
Danio rerio
Subject(s)
Matrix Attachment Region Binding Proteins
Melanoma
Transcription Factors
Access via GEO

Plain Text files from expression profiling by high throughput sequencing
Accession #: GSE77922

Access via SRA

RNA sequencing of 6 samples.
Accession #: SRP070127

Access via BioProject

Additional information about the overall inititative.
Accession #: PRJNA312107

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, SRA and BioProject databases provide open access to these files. SRA and/or tar files can be downloaded directly from the site or viewed in the NCBI SRA Run Selector (link at bottom of page).
Associated Publications
Fazio M, van Rooijen E, Dang M, et al. SATB2 induction of a neural crest mesenchyme-like program drives melanoma invasion and drug resistance. eLife. 2021; 10:e64370.
Data Type
Genomic
Equipment Used
Illumina HiSeq 2500

High throughput sequencing system

Software Used
SRA Toolkit

The NCBI SRA Toolkit enables reading ("dumping") of sequencing files from the SRA database and writing ("loading") files into the .sra format.

Dataset Format(s)
Plain Text, SRA
Data Tool(s)
RNA Seq
Dataset Size
363.5 KB (TXT), 34 GB (SRA)
Data Catalog Record Updated
2023-12-07