E-GEOD-55624 - Inhibiting tankyrases sensitizes KRAS mutant cancer cells to MEK inhibitors by FGFR2 feedback signaling

Status
Released on 6 March 2014, last updated on 3 June 2014
Organism
Homo sapiens
Samples (18)
Array (1)
Protocols (7)
Description
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 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
Experiment type
transcription profiling by array 
Contacts
Joshua M Korn <joshkorn@gmail.com>, Brandon Antonakos, Daisy Flemming, Dmitriy Sonkin, Janine Steiger, Jebediah Ledell, Joseph Lehár, Kristen E Hurov, Marie Schoumacher, Mark Stump, Michael D Jones, Nika N Danial, Vessilina G Cooke, Wenlin Shao, Williams R Sellers, Yan Yan-Neale, Yuji Mishina
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-55624.idf.txt
Sample and data relationshipE-GEOD-55624.sdrf.txt
Raw data (1)E-GEOD-55624.raw.1.zip
Processed data (1)E-GEOD-55624.processed.1.zip
Array designA-AFFY-44.adf.txt
Links