Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly-dividing de-differentiated state
Transcriptomics Dataset
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General Information
AccessionGSE87641
TitleAdaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly-dividing de-differentiated state
DescriptionTreatment of BRAF-mutant melanomas with MAP-kinase pathway inhibitors is paradigmatic of the promise of precision cancer therapy but also highlights problems with drug resistance that limit patient benefit. We use live-cell imaging, single-cell analysis and molecular profiling to show that exposure of tumor cells to RAF/MEK inhibitors elicits a heterogeneous response in which some cells die, some arrest and a remaining fraction adapts to drug. Drug-adapted cells up-regulate markers of the neural crest (e.g. NGFR), a melanocyte precursor, and grow slowly. To identify genes associated with acquisition of the slowly-cycling, vemurafenib-adapted state, we performed RNA sequencing (RNA-seq) on COLO858 cells (that show the slowly-cycling phenotype) exposed to drug for 24 and 48 h; drug-treated MMACSF cells served as a control. Transcriptional profiling implicates a c-Jun/ECM/FAK/Src cascade in adaptive resistance to RAF inhibition.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE87641
RepositoryGene Expression Omnibus
Tools used to analyze the dataset

Dataset Accession

ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
Canned Analyses generated with the dataset

Dataset Accession
Tool Name

Interactive heatmap visualization of RNA-seq dataset GSE87641
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
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