STANDARD_NAME	MAYBURD_RESPONSE_TO_L663536_UP
SYSTEMATIC_NAME	M12002
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/MAYBURD_RESPONSE_TO_L663536_UP
NAMESPACE	AFFY_HG_U133
DESCRIPTION_BRIEF	Genes up-regulated in H720 cells (lung cancer) after treatment with L663536 (MK886) [PubChem=105049], an inhibitor of leukotriene biosynthesis.
DESCRIPTION_FULL	The small molecular inhibitor MK886 is known to block 5-lipoxygenase-activating protein ALOX5AP and shows antitumor activity in multiple human cell lines. The broad antitumor therapeutic window reported in vivo for MK886 in rodents supports further consideration of this structural class. Better understanding of the mode of action of the drug is important for application in humans to take place. Affymetrix microarray study was conducted to explore MK886 pharmacologic mechanism. Ingenuity Pathway Analysis software was applied to validate the results at the transcriptional level by putting them in the context of an experimental proteomic network. Genes most affected by MK886 included actin B and focal adhesion components. A subsequent National Cancer Institute-60 panel study, RT-PCR validation followed by confocal microscopy, and Western blotting also pointed to actin B down-regulation, filamentous actin loss, and disorganization of the transcription machinery. In agreement with these observations, MK886 was found to enhance the effect of UV radiation in H720 lung cancer cell line. In light of the modification of cytoskeleton and cell motility by lipid phosphoinositide 3-kinase products, MK886 interaction with actin B might be biologically important. The low toxicity of MK886 in vivo was modeled and explained by binding and transport by dietary lipids. The rate of lipid absorbance is generally higher for tumors, suggesting a promise of a targeted liposome-based delivery system for this drug. These results suggest a novel antitumor pharmacologic mechanism.
PMID	16551867
GEOID	GSE3202
AUTHORS	Mayburd AL,Martlínez A,Sackett D,Liu H,Shih J,Tauler J,Avis I,Mulshine JL
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1S
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	1552971_at,1552979_at,1556289_at,1556690_s_at,1557774_at,1566966_at,1569577_x_at,205068_s_at,208693_s_at,208723_at,209381_x_at,209610_s_at,209675_s_at,210233_at,212048_s_at,212968_at,214728_x_at,215595_x_at,216071_x_at,217678_at,217789_at,218659_at,218696_at,220324_at,220704_at,220778_x_at,221767_x_at,222982_x_at,223132_s_at,226128_at,227142_at,227902_at,232163_at,236267_at,241399_at,242239_at
GENE_SYMBOLS	SGCZ,LINC00471,,MZF1,RAB17-DT,,LINC02861,ARHGAP26,GARS1,USP11,SF3A2,SLC1A4,HNRNPUL1,IL1RAP,YARS1,RFNG,SMARCA4,,MED12,SLC7A11,SNX6,ASXL2,EIF2AK3,LINC00472,IKZF1,SEMA6B,HDLBP,SLC38A2,TRIM8,BROX,PLEKHG5,GLI4,WDR19,ZNF346,TAFA2,
FOUNDER_NAMES