STANDARD_NAME	NOJIMA_SFRP2_TARGETS_UP
SYSTEMATIC_NAME	M14772
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/NOJIMA_SFRP2_TARGETS_UP
NAMESPACE	AFFY_HG_U133
DESCRIPTION_BRIEF	Cellular proliferation, growth, apoptosis and Wnt signaling genes up-regulated in SNU638 cells (gastric cancer) by overexpression of SFRP2 [GeneID=6423] off a plasmid vector.
DESCRIPTION_FULL	Activation of Wnt signaling has been implicated in gastric tumorigenesis, although mutations in APC (adenomatous polyposis coli), CTNNB1 (beta-catenin) and AXIN are seen much less frequently in gastric cancer (GC) than in colorectal cancer. In the present study, we investigated the relationship between activation of Wnt signaling and changes in the expression of secreted frizzled-related protein (SFRP) family genes in GC. We frequently observed nuclear beta-catenin accumulation (13/15; 87%) and detected the active form of beta-catenin in most (12/16; 75%) GC cell lines. CpG methylation-dependent silencing of SFRP1, SFRP2 and SFRP5 was frequently seen among GC cell lines (SFRP1, 16/16, 100%; SFRP2, 16/16, 100%; SFRP5, 13/16, 81%) and primary GC specimens (SFRP1, 42/46, 91%; SFRP2, 44/46, 96%; SFRP5, 30/46, 65%), and treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine rapidly restored SFRP expression. Ectopic expression of SFRPs downregulated T-cell factor/lymphocyte enhancer factor transcriptional activity, suppressed cell growth and induced apoptosis in GC cells. Analysis of global expression revealed that overexpression of SFRP2 repressed Wnt target genes and induced changes in the expression of numerous genes related to proliferation, growth and apoptosis in GC cells. It thus appears that aberrant SFRP methylation is one of the major mechanisms by which Wnt signaling is activated in GC.
PMID	17297461
GEOID	
AUTHORS	Nojima M,Suzuki H,Toyota M,Watanabe Y,Maruyama R,Sasaki S,Sasaki Y,Mita H,Nishikawa N,Yamaguchi K,Hirata K,Itoh F,Tokino T,Mori M,Imai K,Shinomura Y
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 2
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	117_at,200628_s_at,200690_at,200799_at,200800_s_at,200921_s_at,201464_x_at,201465_s_at,201466_s_at,202014_at,202581_at,202643_s_at,202644_s_at,203725_at,203844_at,206569_at,207536_s_at,207574_s_at,207978_s_at,208791_at,208792_s_at,209101_at,209304_x_at,210587_at,211839_s_at,211936_at,213418_at,214683_s_at,215271_at,217911_s_at,218145_at,219398_at,223121_s_at,223850_at,223919_at,225434_at,227345_at,228846_at,230031_at,240319_at,241840_at,35150_at,36004_at,37028_at
GENE_SYMBOLS	HSPA6,WARS1,HSPA9,HSPA1A,HSPA1A,BTG1,JUN,JUN,JUN,PPP1R15A,HSPA1B,TNFAIP3,TNFAIP3,GADD45A,VHL,IL24,TNFRSF9,GADD45B,NR4A3,CLU,CLU,CCN2,GADD45B,INHBE,CSF1,HSPA5,HSPA6,CLK1,TNN,BAG3,TRIB3,CIDEC,SFRP2,,TP53AIP1,DEDD2,TNFRSF10D,MXD1,HSPA5,,HSPA9,CD40,IKBKG,PPP1R15A
FOUNDER_NAMES	
