STANDARD_NAME MARTIN_VIRAL_GPCR_SIGNALING_DN SYSTEMATIC_NAME M1330 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/MARTIN_VIRAL_GPCR_SIGNALING_DN NAMESPACE MOUSE_SEQ_ACCESSION DESCRIPTION_BRIEF Down-regulated genes in the expression signature of direct and paracrine viral GPCR signaling in endothelial cells. DESCRIPTION_FULL Kaposi's sarcoma (KS) is the most frequent AIDS-associated malignancy, etiologically linked to the infection with the human herpesvirus 8 (HHV-8/KSHV). This member of the gamma-herpesviridae family encodes 81 open reading frames, several bearing oncogenic potential. A constitutively active virally encoded G protein-coupled receptor (vGPCR) readily induces KS-like lesions when expressed in endothelial cells in vivo, and unmasks the oncogenic potential of other HHV-8 genes in a paracrine fashion. How vGPCR causes endothelial cell transformation is still not fully understood. Using full-genome microarray analysis we show here that the expression of nuclear factor-kappaB (NF-kappaB)-regulated genes is a prominent feature triggered by vGPCR in cells expressing this viral oncogene and in cells exposed to vGPCR-induced secretions, thus mimicking its paracrine effect. Indeed, vGPCR activates the NF-kappaB pathway potently, and NF-kappaB activation is a hallmark of both human and experimental KS. Of interest, whereas constitutive NF-kappaB signaling is not sufficient to promote endothelial cells transformation, NF-kappaB function is strictly required for vGPCR-induced direct and paracrine neoplasia. Taken together, these results strongly support the role of NF-kappaB regulated genes in KS pathogenesis, thus providing the rationale for the development of novel mechanism-based therapies for this angioproliferative disease. PMID 17934524 GEOID AUTHORS Martin D,Galisteo R,Ji Y,Montaner S,Gutkind JS CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG Broad Institute EXACT_SOURCE Table S1B FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS BC098230,NM_001002005,NM_001002896,NM_001003920,NM_001033274,NM_001033409,NM_001039474,NM_001081249,NM_007546,NM_007911,NM_007957,NM_008549,NM_008827,NM_009214,NM_009888,NM_010235,NM_010391,NM_010414,NM_010482,NM_010738,NM_011552,NM_011790,NM_012045,NM_012058,NM_013702,NM_017111,NM_019388,NM_019441,NM_019473,NM_019485,NM_019578,NM_019636,NM_019698,NM_021491,NM_025444,NM_025485,NM_026666,NM_028757,NM_028883,NM_029098,NM_030609,NM_133900,NM_133977,NM_144523,NM_144783,NM_145148,NM_145916,NM_146701,NM_146867,NM_147015,NM_172729,NM_175096,NM_175114,NM_175136,NM_199011,XM_135242 GENE_SYMBOLS LSM6,PANX2,BFSP2,BRSK1,BRD1,LGR6,TCERG1,VCAN,BIK,EFNB3,ESX1,MAN2A1,PGF,SMS,CFH,FOSL1,HLA-A,HTT,HTR1B,,TCOF1,ARIH2,PLA2G2F,SRP9,UNCX,SLCO1A2,CD86,PPT2,OR13C7,,EXTL1,TBC1D1,ALDH18A1,SMPD3,TAF13,MRPS22,UBN1,NEBL,MEAK7,LMBR1L,H1-1,PSPH,TF,ZNF622,WT1,FRMD4B,ZNF7,OR5B12,,OR5AR1,NOD1,STBD1,TRAK1,RNF122,DGKQ, FOUNDER_NAMES