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Series GSE55624 Query DataSets for GSE55624
Status Public on Mar 06, 2014
Title Inhibiting tankyrases sensitizes KRAS mutant cancer cells to MEK inhibitors by FGFR2 feedback signaling
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Tankyrases (TNKS) play roles in Wnt signaling, telomere homeostasis and mitosis, offering attractive targets for anti-cancer treatment. Using unbiased combination screening in a large panel of cancer cell lines, we have identified a strong synergy between TNKS and MEK inhibitors in KRAS mutant cancer cells. Our study uncovers a novel function of TNKS in the relief of a feedback loop induced by MEK inhibition on FGFR2 signaling pathway. Moreover, dual inhibition of TNKS and MEK leads to more robust apoptosis and anti-tumor activity both in vitro and in vivo than effects observed by previously reported MEK inhibitor combinations. Altogether, our results show how a novel combination of TNKS and MEK inhibitors can be highly effective in targeting KRAS mutant cancers by suppressing a newly discovered resistance mechanism.
This experiment is designed to detect genes differentially expressed in the combination treatment compared to others
Overall design SW480 cells were seeded in 10cm dishes and treated for 4h and 16h with DMSO, TNKS inhibitor (TNKSi : NVP-TNKS656), MEK inhibitor (MEKi : AZD6244) or the combination of both at 1uM final
Contributor(s) Schoumacher M, Hurov KE, Lehár J, Yan-Neale Y, Mishina Y, Sonkin D, Korn JM, Flemming D, Jones MD, Antonakos B, Cooke VG, Steiger J, Ledell J, Stump M, Sellers WR, Danial NN, Shao W
Citation(s) 24747911
Submission date Mar 05, 2014
Last update date Mar 25, 2019
Contact name Joshua M Korn
Organization name Novartis
Street address 250 Mass Ave
City Cambridge
State/province MA
ZIP/Postal code 02141
Country USA
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (18)
GSM1340521 parental biological replicate 1
GSM1340522 parental biological replicate 2
GSM1340523 DMSO 4h biological replicate 1
BioProject PRJNA240233

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE55624_RAW.tar 92.1 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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