Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA478296 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7465040.fastq.gz | Fastqsanger.gz | |||
| SRR7465041.fastq.gz | Fastqsanger.gz | |||
| SRR7465042.fastq.gz | Fastqsanger.gz | |||
| SRR7465043.fastq.gz | Fastqsanger.gz | |||
| SRR7465044.fastq.gz | Fastqsanger.gz |
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Project description:Metastasis is a complex process involving loss of adhesion, migration, invasion and proliferation of cancer cells. Cell adhesion molecules play a pivotal role in this phenomenon by regulating cell-cell and cell-matrix interactions. CD146 (MCAM) is associated with advanced tumor stage in melanoma, prostate and ovarian cancers. For this study, the MDA-MB-231 cell line was used as a prototypic mesenchymal and invasive cell line, spontaneously expressing high levels of CD146. Using whole-genome DNA microarrays, we investigated genes for which expression was modified by CD146 down-regulation, obtained by siRNA or shRNA technology Experiment Overall Design: Expression profiles of two cell lines transfected by two differents ShRNA directed against CD146 were compared with expression profiles of 3 control cell lines (i.e. native cell line, empty plasmid and shRNA directed against GFP)
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Project description:In this study, we show that histone variant H3.3 is overexpressed in ARMS patient-derived cell lines and patient tumour specimens. Functionally, knockdown of H3F3A significantly impairs the ability of ARMS cells to undertake migration and invasion and reduces Rho activation in vitro. In addition, a striking reduction in metastatic tumour burden and improved survival is apparent in vivo. Through RNA-sequencing and ChIP-sequencing analyses, we identified Melanoma Cell Adhesion Molecule (MCAM/CD146) as a direct downstream target of H3.3. Therefore, this study identifies a novel H3.3- MCAM axis involved in ARMS metastatic phenotypes, and supports the development of MCAM as a therapeutic target for this disease.
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