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Series GSE134320 Query DataSets for GSE134320
Status Public on Jul 16, 2019
Title Treatment of melanoma cell lines with CCG-222740
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary The Ras/MEK/ERK pathway has been the primary focus of targeted therapies in melanoma, given that it is aberrantly activated in almost 80% of human cutaneous melanomas (~50% BRAFV600 mutations and ~30% NRAS mutations). While targeted therapies have yielded success in BRAFV600 mutant melanoma patients, such therapies have been ineffective in NRAS mutant melanomas in part due to their cytostatic effects and primary resistance in this patient population. Here, we demonstrate that increased Rho/MRTF-pathway activation correlates with high intrinsic resistance to trametinib, a MEK inhibitor, in a panel of NRAS mutant melanoma cell lines. Combination of trametinib with the Rho/MRTF-pathway inhibitor, CCG-222740, synergistically reduced cell viability in NRAS mutant melanoma cell lines in vitro. Furthermore, the combination of CCG-222740 with trametinib induced apoptosis and reduced clonogenicity in the highly trametinib-resistant SK-Mel-147 cells. These findings suggest a role of the Rho/MRTF-pathway in high intrinsic trametinib resistance to a subset of NRAS mutant melanoma cell lines and highlights the potential of concurrently targeting the Rho/MRTF-pathway and MEK in NRAS mutant melanomas.
Overall design Melanoma cell lines were treated with the MRTF pathway inhibitor CCG-222740 and RNA-Seq was performed to measure gene expression.
mRNA profiles of various melanoma cell lines treated with 10 uM CCG-222740 for 0, 2, 6, or 24 hours.
Contributor(s) Misek S, Neubig R
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Submission date Jul 15, 2019
Last update date Jul 18, 2019
Contact name Sean Alexander Misek
Organization name Michigan State University
Street address 1355 Bogue Street
City East Lansing
State/province MI
ZIP/Postal code 48823
Country USA
Platforms (1)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (40)
GSM3942131 SKMel2_0h_N1
GSM3942132 SKMel2_0h_N2
GSM3942133 SKMel2_2h_N1
BioProject PRJNA554700
SRA SRP214725

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Supplementary file Size Download File type/resource
GSE134320_RAW.tar 8.3 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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