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<MSIGDB BUILD_DATE="Jan 29, 2026" VERSION="2026.1.Hs" NAME="export">
    <GENESET STANDARD_NAME="YAN_ESCAPE_FROM_ANOIKIS" SYSTEMATIC_NAME="M1221" HISTORICAL_NAMES="" PMID="16007176" AUTHORS="Yan SR,Joseph RR,Rosen K,Reginato MJ,Jackson A,Allaire N,Brugge JS,Jobin C,Stadnyk AW" GEOID="" EXACT_SOURCE="Table 1S" GENESET_LISTING_URL="" EXTERNAL_DETAILS_URL="" CHIP="RAT_SEQ_ACCESSION" CONTRIBUTOR="Arthur Liberzon" CONTRIBUTOR_ORG="MSigDB Team" 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." TAGS="" 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" MEMBERS_SYMBOLIZED="ALDH3A1,BCL2L11,C2,CCL20,CCL5,CD44,CX3CL1,CXCL10,DDIT3,EIF2AK2,HLA-DMA,IL15,IRF1,IRF7,LTA,MMP2,MX1,NFKB1,NOS2,RSAD2,STAT1,STAT2,VCAM1" MEMBERS_EZID="10018,1649,218,3108,3600,3627,3659,3665,4049,4313,4599,4790,4843,5610,6352,6364,6376,6772,6773,717,7412,91543,960" MEMBERS_MAPPING="AA799569,STAT2,6773|AA799861,IRF7,3665|AA891944,null,null|AA892553,STAT1,6772|AA926129,null,null|AF030358,CX3CL1,6376|AF053312,CCL20,6364|AF065433,BCL2L11,10018|AI009658,CCL5,6352|AI232284,null,null|AI235890,null,null|AI639117,C2,717|J03637,ALDH3A1,218|L00981,LTA,4049|L23128,null,null|L26267,NFKB1,4790|L29281,EIF2AK2,5610|M34253,IRF1,3659|M61875,CD44,960|M84488,VCAM1,7412|U03699,NOS2,4843|U17035,CXCL10,3627|U30186,DDIT3,1649|U31598,HLA-DMA,3108|U65656,MMP2,4313|U69272,IL15,3600|X52711,MX1,4599|Y07704,RSAD2,91543" FILTERED_BY_SIMILARITY="" FOUNDER_NAMES="" REFINEMENT_DATASETS="" VALIDATION_DATASETS="" CATEGORY_CODE="C2" ORGANISM="Rattus norvegicus" SUB_CATEGORY_CODE="CGP"/>
</MSIGDB>
