STANDARD_NAME MITSIADES_RESPONSE_TO_APLIDIN_UP SYSTEMATIC_NAME M7928 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/MITSIADES_RESPONSE_TO_APLIDIN_UP NAMESPACE AFFY_HG_U133 DESCRIPTION_BRIEF Genes up-regulated in the MM1S cells (multiple myeloma) after treatment with aplidin [PubChem=44152164], a marine-derived compound with potential anti-cancer properties. DESCRIPTION_FULL Despite recent progress in its treatment, multiple myeloma (MM) remains incurable, thus necessitating identification of novel anti-MM agents. We report that the marine-derived cyclodepsipeptide Aplidin exhibits, at clinically achievable concentrations, potent in vitro activity against primary MM tumor cells and a broad spectrum of human MM cell lines, including cells resistant to conventional (e.g., dexamethasone, alkylating agents, and anthracyclines) or novel (e.g., thalidomide and bortezomib) anti-MM agents. Aplidin is active against MM cells in the presence of proliferative/antiapoptotic cytokines or bone marrow stromal cells and has additive or synergistic effects with some of the established anti-MM agents. Mechanistically, a short in vitro exposure to Aplidin induces MM cell death, which involves activation of p38 and c-jun NH(2)-terminal kinase signaling, Fas/CD95 translocation to lipid rafts, and caspase activation. The anti-MM effect of Aplidin is associated with suppression of a constellation of proliferative/antiapoptotic genes (e.g., MYC, MYBL2, BUB1, MCM2, MCM4, MCM5, and survivin) and up-regulation of several potential regulators of apoptosis (including c-JUN, TRAIL, CASP9, and Smac). Aplidin exhibited in vivo anti-MM activity in a mouse xenograft model. The profile of the anti-MM activity of Aplidin in our preclinical models provided the framework for its clinical testing in MM, which has already provided favorable preliminary results. PMID 18593922 GEOID AUTHORS Mitsiades CS,Ocio EM,Pandiella A,Maiso P,Gajate C,Garayoa M,Vilanova D,Montero JC,Mitsiades N,McMullan CJ,Munshi NC,Hideshima T,Chauhan D,Aviles P,Otero G,Faircloth G,Mateos MV,Richardson PG,Mollinedo F,San-Miguel JF,Anderson KC CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 3S FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 200673_at,200759_x_at,200788_s_at,200797_s_at,200798_x_at,200838_at,200839_s_at,200867_at,200904_at,200924_s_at,200997_at,201044_x_at,201060_x_at,201061_s_at,201096_s_at,201097_s_at,201146_at,201174_s_at,201289_at,201471_s_at,201502_s_at,201557_at,201565_s_at,201583_s_at,201601_x_at,201620_at,201648_at,201666_at,201669_s_at,201703_s_at,201717_at,201734_at,201735_s_at,201751_at,201844_s_at,201870_at,201878_at,201881_s_at,201995_at,202021_x_at,202068_s_at,202130_at,202131_s_at,202140_s_at,202146_at,202165_at,202166_s_at,202181_at,202241_at,202301_s_at,202302_s_at,202310_s_at,202334_s_at,202388_at,202391_at,202446_s_at,202464_s_at,202492_at,202531_at,202560_s_at,202577_s_at,202637_s_at,202638_s_at,202695_s_at,202703_at,202710_at,202724_s_at,202725_at,202768_at,202869_at,202902_s_at,202918_s_at,202919_at,202928_s_at,202933_s_at,202973_x_at,203011_at,203053_at,203068_at,203090_at,203097_s_at,203153_at,203217_s_at,203288_at,203298_s_at,203301_s_at,203312_x_at,203330_s_at,203335_at,203380_x_at,203395_s_at,203397_s_at,203476_at,203480_s_at,203569_s_at,203583_at,203610_s_at,203616_at,203725_at,203752_s_at,203775_at,203816_at,203821_at,203852_s_at,203921_at,203946_s_at,203965_at,203984_s_at,203986_at,203989_x_at,204148_s_at,204155_s_at,204157_s_at,204174_at,204187_at,204194_at,204222_s_at,204253_s_at,204266_s_at,204276_at,204284_at,204288_s_at,204382_at,204406_at,204420_at,204434_at,204472_at,204523_at,204567_s_at,204611_s_at,204615_x_at,204630_s_at,204640_s_at,204645_at,204698_at,204719_at,204735_at,204739_at,204760_s_at,204794_at,204805_s_at,204891_s_at,204908_s_at,204937_s_at,204957_at,205025_at,205114_s_at,205192_at,205193_at,205214_at,205239_at,205246_at,205249_at,205278_at,205281_s_at,205288_at,205306_x_at,205398_s_at,205548_s_at,205632_s_at,205660_at,205664_at,205713_s_at,205807_s_at,205967_at,206082_at,206121_at,206175_x_at,206249_at,206300_s_at,206307_s_at,206382_s_at,206598_at,206648_at,206683_at,206769_at,206844_at,206907_at,206978_at,207001_x_at,207266_x_at,207351_s_at,207571_x_at,207574_s_at,207630_s_at,207734_at,207760_s_at,207768_at,207826_s_at,207978_s_at,208066_s_at,208093_s_at,208094_s_at,208105_at,208129_x_at,208249_s_at,208436_s_at,208490_x_at,208496_x_at,208523_x_at,208536_s_at,208623_s_at,208685_x_at,208686_s_at,208786_s_at,208810_at,208831_x_at,208836_at,208869_s_at,208881_x_at,208891_at,208895_s_at,208896_at,208922_s_at,208924_at,208925_at,208942_s_at,208960_s_at,208961_s_at,209020_at,209034_at,209069_s_at,209102_s_at,209122_at,209161_at,209180_at,209181_s_at,209185_s_at,209300_s_at,209304_x_at,209305_s_at,209309_at,209326_at,209344_at,209355_s_at,209383_at,209403_at,209457_at,209481_at,209524_at,209541_at,209549_s_at,209573_s_at,209578_s_at,209606_at,209751_s_at,209806_at,209845_at,209868_s_at,209906_at,209912_s_at,209959_at,209999_x_at,210041_s_at,210069_at,210090_at,210113_s_at,210170_at,210223_s_at,210241_s_at,210258_at,210346_s_at,210370_s_at,210401_at,210426_x_at,210561_s_at,210722_at,210764_s_at,210805_x_at,210910_s_at,211024_s_at,211138_s_at,211142_x_at,211191_at,211382_s_at,211423_s_at,211692_s_at,211763_s_at,211997_x_at,211999_at,212096_s_at,212099_at,212111_at,212130_x_at,212203_x_at,212226_s_at,212227_x_at,212230_at,212232_at,212288_at,212383_at,212436_at,212458_at,212501_at,212503_s_at,212522_at,212614_at,212689_s_at,212700_x_at,212717_at,212722_s_at,212723_at,212733_at,212770_at,212816_s_at,212912_at,212935_at,212939_at,212961_x_at,212975_at,212977_at,213000_at,213021_at,213024_at,213026_at,213034_at,213112_s_at,213146_at,213161_at,213281_at,213315_x_at,213324_at,213331_s_at,213341_at,213387_at,213452_at,213769_at,213858_at,213940_s_at,213959_s_at,213990_s_at,214016_s_at,214056_at,214112_s_at,214150_x_at,214152_at,214157_at,214179_s_at,214290_s_at,214329_x_at,214429_at,214430_at,214463_x_at,214472_at,214502_at,214522_x_at,214542_x_at,214559_at,214582_at,214683_s_at,214696_at,214714_at,214749_s_at,214787_at,214791_at,214829_at,214911_s_at,215009_s_at,215412_x_at,215426_at,215440_s_at,215441_at,215498_s_at,215499_at,215667_x_at,215693_x_at,215967_s_at,215982_s_at,216061_x_at,216078_at,216236_s_at,216357_at,216425_at,216585_at,216846_at,216958_s_at,217028_at,217127_at,217168_s_at,217174_s_at,217222_at,217264_s_at,217362_x_at,217591_at,217672_x_at,217682_at,217722_s_at,217738_at,217739_s_at,217836_s_at,217858_s_at,217892_s_at,217996_at,218004_at,218012_at,218017_s_at,218023_s_at,218064_s_at,218094_s_at,218100_s_at,218107_at,218192_at,218311_at,218321_x_at,218336_at,218347_at,218373_at,218375_at,218378_s_at,218411_s_at,218449_at,218459_at,218478_s_at,218539_at,218572_at,218631_at,218649_x_at,218696_at,218721_s_at,218769_s_at,218773_s_at,218776_s_at,218819_at,218872_at,218914_at,218929_at,218946_at,218955_at,218964_at,218972_at,218987_at,218997_at,219017_at,219033_at,219099_at,219108_x_at,219128_at,219147_s_at,219195_at,219231_at,219336_s_at,219350_s_at,219357_at,219368_at,219371_s_at,219398_at,219406_at,219474_at,219499_at,219551_at,219647_at,219655_at,219734_at,219755_at,219801_at,219862_s_at,219889_at,219911_s_at,219949_at,220046_s_at,220059_at,220123_at,220185_at,220214_at,220319_s_at,220330_s_at,220370_s_at,220387_s_at,220494_s_at,220606_s_at,220755_s_at,220822_at,220933_s_at,220987_s_at,220992_s_at,221230_s_at,221471_at,221493_at,221511_x_at,221530_s_at,221559_s_at,221580_s_at,221641_s_at,221686_s_at,221699_s_at,221756_at,221766_s_at,221773_at,221778_at,221786_at,221803_s_at,221808_at,221821_s_at,221841_s_at,221842_s_at,221854_at,221887_s_at,221899_at,221911_at,221962_s_at,222001_x_at,222067_x_at,222068_s_at,222071_s_at,222156_x_at,222199_s_at,222200_s_at,222243_s_at,222379_at,33304_at,37028_at,38157_at,40446_at,41329_at,41386_i_at,47530_at,47608_at,62212_at,64432_at GENE_SYMBOLS LAPTM4A,NFE2L1,PEA15,MCL1,MCL1,CTSB,CTSB,RNF114,HLA-E,SLC3A2,RBM4,DUSP1,STOM,STOM,ARF4,ARF4,NFE2L2,TERF2IP,CCN1,SQSTM1,NFKBIA,VAMP2,ID2,SEC23B,IFITM1,MBTPS1,JAK1,TIMP1,MARCKS,PPP1R10,MRPL49,CLCN3,CLCN3,JOSD1,RYBP,TOMM34,ARIH1,ARIH1,EXT1,EIF1,LDLR,RIOK3,RIOK3,CLK3,IFRD1,PPP1R2,PPP1R2,SUSD6,TRIB1,RSRC2,RSRC2,COL1A1,UBE2B,RGS2,BASP1,PLSCR1,PFKFB3,ATG9A,IRF1,CHTOP,DDX19A,ICAM1,ICAM1,STK17A,DUSP11,BET1,FOXO1,POLR2A,FOSB,OAS1,CTSS,MOB4,MOB4,PHF1,YES1,FAM13A,IMPA1,BCAS2,KLHL21,SDF2,RAPGEF2,IFIT1,ST3GAL5,GARRE1,JARID2,DMTF1,ARF6,STX5,PHYH,SRSF5,HES1,GALNT3,TPBG,OTUD4,OFD1,UNC50,TRIM38,POLB,GADD45A,JUND,SLC25A13,DGUOK,HBEGF,SMN1,CHST2,ARG2,USP20,CASP9,STBD1,F2R,ZP3,SIK3,SIK3,ALOX5AP,GMPR,BACH1,GLIPR1,VDR,CHKA,TK2,PPP1R3C,SORBS2,NAT9,,FOSL1,SPATA2,GEM,ZNF140,ABCG1,PPP2R5B,IDI1,GOSR1,SPOP,CCNT2,ISG20,ABCA8,PDE4A,CENPC,NR1D1,DUSP2,H1-10,LCK,BCL3,ZNF274,ORC5,ZBTB48,CCL3,MAP3K14,MAFF,STK17B,AREG,PEX13,,GAD1,PIGA,CDC14A,KMO,SMAD3,BTG3,PIP5K1B,OASL,KIN,COMP,TUFT1,H4C3,HCP5,AMPD1,ZNF222,MAP3K13,PTHLH,FOXD1,BDNF,INS,ZNF571,ZNF165,TMSB4Y,FBP2,TNFSF9,CCR2,TSC22D3,RBMS1,SH2D2A,THEMIS2,GADD45B,CREM,LAX1,NCOR2,EGR4,ID3,NR4A3,GTF2B,NDEL1,YJU2B,GIPR,RUNX1,TGDS,IRF7,H2BC7,H2AC10P,H2BC10,BCL2L11,EZR,BRD2,BRD2,MAP1LC3B,DNAJB6,SUPT6H,ATP1B3,GABARAPL1,IDI1,DUSP6,DDX18,DDX18,NXF1,RNF11,CLDND1,SEC62,KLF6,KLF6,OSER1,PNRC1,H3-3B,HBP1,PLIN2,PRPF4,RABGGTB,RABGGTB,IRS2,NECAP1,GADD45B,GADD45B,AZGP1,SLC35A2,TPM4,PLPP3,DDIT3,TBC1D3F,DUSP5,SNRK,HDGFL3,IGF1,DGUOK,LDLRAD4,POFUT2,CYTIP,TRAPPC2,,MKRN1,RBMS1,C3AR1,AP5Z1,NR4A3,SOCS1,PGM3,CPT1B,ARC,NLRP1,PDLIM3,MR1,TP53TG1,RGS13,CLK4,LY9,P2RX1,RORA,WSB1,PNLIPRP1,CCN1,RUNX1,ZP3,NKX2-1,KMO,HLA-DOA,CD84,TACC2,SC5D,BBC3,UBE2B,H3-3B,H3-3B,MTUS1,RHOB,STX12,EIF1,IFITM3,PLPP3,EIF1,PLPP3,FNBP4,FNBP1,ATP6V0A1,TRIM33,SPRED2,CEBPB,DIP2C,PDE8A,ARID5B,KDM3A,PLEKHM1,PLEKHM1,JMJD6,JMJD6,RUBCN,TLE3,CBS,RPS6KA2,MCF2L,,EOLA1,DENND3,ACKR3,MORC3,GOSR1,TMF1,ATG12,SIK3,SQSTM1,KDM6B,TSTD2,,EOLA1,SRC,NEK1,FEM1C,ATAD2B,ZNF184,KSR1,ZNF250,FNBP1,RPGRIP1L,PAK5,SFPQ,,EOLA1,ATP6V0E1,CCPG1,GNAS,NFE2L1,H2AC18,TNFSF10,MTMR6,GLA,H4C12,H3C4,,H2AC7,H2AC13,DRD3,PDE3B,CLK1,MIR22HG,ZNF394,ARMCX6,DENND4A,SP140L,AASS,BRD2,THAP9-AS1,PMS2P2,,BEX4,,MAP2K3,MAP2K3,PMS2P2,DDX27,LY9,DXO,PDGFB,,SLC2A3,,,H2AC10P,,IVD,CXCR4,CTH,HERPUD1,APC2,,SCNN1A,HLA-DRB6,SKIL,,HAPSTR1,NGRN,NAMPT,NAMPT,YY1AP1,ARMCX3,LIMA1,NAP1L1,BSDC1,TSPYL2,HGSNAT,FAM53C,AKAP8L,DBNDD2,IFT57,WDR26,IP6K2,MAP4K3,STYXL1,PFDN2,TYW1,AKTIP,NUDT9,PRKRIP1,MBIP,UFSP2,TOR3A,ZCCHC8,FBXO34,CHMP4A,AVPI1,NEMF,EIF2AK3,ODR4,ANKRA2,MSRB2,CCNDBP1,INTS6,TESC,METTL25B,CDKN2AIP,NFU1,BRF2,ARID3B,TTC17,ATF7IP,POLR1E,ETNK1,PARP8,TIGAR,DDX27,C2orf42,NMRK1,PPARGC1A,TGS1,ASCC1,DIABLO,GTPBP1,NAP1L2,KLF2,CIDEC,C1orf50,C3orf52,SEC61A2,EAF2,POPDC2,SUGCT,SIDT1,CBX8,ZNF34,NARF,FRAT1,SLCO4A1,LRRC2,CCNL1,STAP1,SLC35F5,SPTBN4,ZNF215,MYLIP,SAMSN1,USP36,HHLA3,,ADPRM,SNHG32,,TUT7,NUAK2,TRMT1L,ARID4B,SERINC3,TSPYL1,CCPG1,BHLHE41,MIS12,TAF1D,ACOT9,RECQL5,DDX50,PIK3IP1,TENT5A,ELK3,KDM7A,C6orf120,NRBF2,RAB9A,KANSL2,KLF4,ZNF131,PKP1,WHRN,N4BP2L2,ETV1,UBE2H,LINC00869,H2BC5,DNAAF1,SLCO4C1,CCPG1,BIN3,BSDC1,TOB2,KCNE4,ISG20,PPP1R15A,DXO,PHF1,SCYL3,KDM6B,TRMO,TJAP1,C1orf50,MAPKAPK5-AS1 FOUNDER_NAMES