STANDARD_NAME	YAN_ESCAPE_FROM_ANOIKIS
SYSTEMATIC_NAME	M1221
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/YAN_ESCAPE_FROM_ANOIKIS
NAMESPACE	RAT_SEQ_ACCESSION
DESCRIPTION_BRIEF	Genes up-regulated in IEC-18 cells (intestinal epithelial cells) which avoided anoikis (a form of apoptosis) after detachment.
DESCRIPTION_FULL	We reported earlier that IL-1beta, an NF-kappaB-regulated cytokine, was made by intestinal epithelial cells during detachment-induced apoptosis (anoikis) and that IL-1 was antiapoptotic for detached cells. Since surviving anoikis is a prerequisite for cancer progression and metastases, we are further exploring the link between anoikis and cytokines. Here we determined that multiple genes are expressed following detachment including a number of NF-kappaB-regulated products and therefore aimed to determine whether NF-kappaB signalling plays any role in regulating apoptosis. Using Western blotting, we detected that IkappaBalpha becomes phosphorylated immediately following detachment and that levels of phospho-IkappaBalpha peaked within 20 min. Phosphorylation of IkappaBalpha was followed by Rel A (p65) nuclear translocation. Increased NF-kappaB activity following detachment was confirmed using the detection of NF-kappaB-promoted luciferase gene expression delivered by adenovirus infection. Infection of cells with adenovirus expressing a super-repressor IkappaBalpha protein and pharmacological inhibitors of NF-kappaB resulted in the failure to phosphorylate IkappaBalpha, a more rapid activation of caspases and earlier apoptosis. We also detected that IkappaB kinase alpha (IKKalpha) and not IKKbeta became phosphorylated following detachment. Since IKKalpha is activated by NF-kappaB-inducing kinase (NIK), we overexpressed native NIK using an adenovirus vector that resulted in enhanced phospho-IkappaBalpha and nuclear p65 in detached cells compared to control detached cells but did not result in a significantly greater number of cells surviving to 24 h. We conclude that detachment directly activates NF-kappaB, which, in addition to launching an inflammatory cytokine wave, contributes to a delay in apoptosis in intestinal epithelial cells.
PMID	16007176
GEOID	
AUTHORS	Yan SR,Joseph RR,Rosen K,Reginato MJ,Jackson A,Allaire N,Brugge JS,Jobin C,Stadnyk AW
CONTRIBUTOR	Arthur Liberzon
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Table 1S
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	AA799569,AA799861,AA891944,AA892553,AA926129,AF030358,AF053312,AF065433,AI009658,AI232284,AI235890,AI639117,J03637,L00981,L23128,L26267,L29281,M34253,M61875,M84488,U03699,U17035,U30186,U31598,U65656,U69272,X52711,Y07704
GENE_SYMBOLS	STAT2,IRF7,,STAT1,,CX3CL1,CCL20,BCL2L11,CCL5,,,C2,ALDH3A1,LTA,,NFKB1,EIF2AK2,IRF1,CD44,VCAM1,NOS2,CXCL10,DDIT3,HLA-DMA,MMP2,IL15,MX1,RSAD2
FOUNDER_NAMES