STANDARD_NAME YAUCH_HEDGEHOG_SIGNALING_PARACRINE_DN SYSTEMATIC_NAME M9331 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/YAUCH_HEDGEHOG_SIGNALING_PARACRINE_DN NAMESPACE AFFY_Mouse430 DESCRIPTION_BRIEF Genes down-regulated in mouse stroma of pancreatic adenocarcinoma zenografts after treatment with HhAntag, a hedgehog (Hh) pathway inhibitor. DESCRIPTION_FULL Ligand-dependent activation of the hedgehog (Hh) signalling pathway has been associated with tumorigenesis in a number of human tissues. Here we show that, although previous reports have described a cell-autonomous role for Hh signalling in these tumours, Hh ligands fail to activate signalling in tumour epithelial cells. In contrast, our data support ligand-dependent activation of the Hh pathway in the stromal microenvironment. Specific inhibition of Hh signalling using small molecule inhibitors, a neutralizing anti-Hh antibody or genetic deletion of smoothened (Smo) in the mouse stroma results in growth inhibition in xenograft tumour models. Taken together, these studies demonstrate a paracrine requirement for Hh ligand signalling in the tumorigenesis of Hh-expressing cancers and have important implications for the development of Hh pathway antagonists in cancer. PMID 18754008 GEOID GSE11981 AUTHORS Yauch RL,Gould SE,Scales SJ,Tang T,Tian H,Ahn CP,Marshall D,Fu L,Januario T,Kallop D,Nannini-Pepe M,Kotkow K,Marsters JC,Rubin LL,de Sauvage FJ CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Supplmentary File 2: pvalue<0.05 and log2(Fold Change) < -1.5 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS 1415924_at,1416063_x_at,1416413_at,1416711_at,1416889_at,1417256_at,1417464_at,1417489_at,1417614_at,1417653_at,1418129_at,1418155_at,1418314_a_at,1418487_at,1418588_at,1418726_a_at,1418766_s_at,1418818_at,1419014_at,1419082_at,1419096_at,1419145_at,1419150_at,1419151_at,1419312_at,1419474_a_at,1419717_at,1419801_x_at,1419890_at,1419933_at,1419937_at,1420009_at,1420188_at,1420239_x_at,1420258_at,1420312_s_at,1420418_at,1420436_x_at,1420553_x_at,1420574_at,1420757_at,1420764_at,1420778_at,1420884_at,1421246_at,1421398_at,1421515_at,1421700_at,1422016_a_at,1422071_at,1422166_at,1422217_a_at,1422229_at,1422235_at,1422309_a_at,1422348_at,1422423_at,1422427_a_at,1422448_at,1422529_s_at,1422588_at,1422644_at,1422917_at,1423604_at,1424226_at,1424404_at,1424900_at,1425063_at,1425254_at,1425301_at,1425416_s_at,1425450_at,1425540_at,1425744_a_at,1425772_at,1425953_at,1425963_at,1426134_at,1426142_a_at,1426144_x_at,1426638_at,1427026_at,1427141_at,1427315_at,1427445_a_at,1427446_s_at,1427507_at,1427519_at,1427520_a_at,1427532_at,1427562_a_at,1427629_at,1427722_at,1427735_a_at,1427767_a_at,1427778_at,1427868_x_at,1427872_at,1428059_at,1428183_at,1428722_at,1429023_at,1429228_at,1429309_at,1429354_at,1429386_at,1429645_at,1429688_at,1429757_at,1429851_at,1430099_at,1430243_at,1430244_at,1430247_at,1430248_at,1430398_at,1430475_at,1430551_s_at,1430581_at,1430667_at,1430684_s_at,1430685_at,1430742_a_at,1430879_at,1431014_at,1431093_at,1431439_at,1431536_at,1431648_at,1431651_at,1431795_a_at,1431903_at,1431911_at,1431981_at,1432067_at,1432077_at,1432105_at,1432148_at,1432198_at,1432452_at,1432463_at,1432559_at,1432591_at,1432619_at,1432833_at,1432901_at,1432914_at,1433007_at,1433009_at,1433094_at,1433188_at,1433200_at,1433229_at,1433373_at,1433458_at,1434347_s_at,1434719_at,1434734_at,1435145_at,1435209_at,1435239_at,1435252_at,1435355_at,1435393_at,1435813_at,1435831_at,1435951_at,1436148_at,1436274_at,1436374_x_at,1436579_s_at,1436613_at,1436794_at,1437086_at,1437130_at,1437258_at,1437272_at,1437440_at,1437452_x_at,1437515_at,1437534_at,1437602_at,1437609_at,1437860_at,1437880_at,1437988_x_at,1437998_at,1438020_at,1438054_x_at,1438059_at,1438060_at,1438119_at,1438145_at,1438150_at,1438175_x_at,1438224_at,1438348_x_at,1438362_x_at,1438388_at,1438395_at,1438461_at,1438470_at,1438609_x_at,1438618_at,1438636_s_at,1438704_at,1438717_a_at,1438837_at,1438850_at,1438856_x_at,1438885_at,1438970_x_at,1439086_at,1439096_at,1439334_at,1439402_at,1439543_at,1439581_at,1439627_at,1439654_at,1439691_at,1439709_at,1439729_at,1439756_at,1439760_x_at,1439836_at,1439870_at,1439987_at,1440063_at,1440101_at,1440429_at,1440468_at,1440508_at,1440598_at,1440617_at,1440673_at,1440710_at,1440910_at,1440932_at,1441088_at,1441353_at,1441374_at,1441550_at,1441623_at,1441830_x_at,1441858_at,1441935_at,1442032_at,1442110_at,1442215_at,1442281_at,1442419_at,1442456_at,1442516_at,1442558_at,1442580_at,1442675_at,1442724_at,1442879_at,1442889_at,1442895_at,1442937_at,1442938_at,1443014_at,1443074_at,1443117_at,1443264_at,1443342_at,1443364_at,1443437_at,1443448_x_at,1443457_at,1443473_at,1443561_at,1443571_at,1443616_at,1443703_at,1443705_at,1443788_at,1443834_at,1443858_at,1443994_at,1444129_at,1444142_at,1444250_at,1444270_at,1444424_at,1444494_at,1444571_at,1444591_at,1444743_at,1444817_at,1444841_at,1444986_at,1445019_at,1445030_at,1445053_at,1445089_at,1445156_at,1445188_at,1445219_at,1445287_at,1445352_at,1445384_at,1445564_at,1445576_at,1445592_at,1445648_at,1445740_at,1445841_at,1445920_at,1445925_at,1445991_at,1445992_at,1446113_at,1446151_at,1446183_at,1446243_at,1446327_at,1446502_at,1446523_at,1446532_at,1446572_at,1446597_at,1446611_at,1446713_at,1446742_at,1446792_at,1446842_at,1446864_at,1446916_at,1446986_at,1447066_at,1447116_at,1447141_at,1447163_x_at,1447265_at,1447437_at,1447473_at,1447502_at,1447508_at,1447536_at,1447545_at,1447616_at,1447637_at,1447655_x_at,1447683_x_at,1447698_x_at,1448074_at,1448327_at,1448371_at,1448544_at,1448602_at,1448686_at,1448690_at,1448764_a_at,1449178_at,1449388_at,1449430_a_at,1449526_a_at,1449539_at,1449544_a_at,1449594_at,1449879_at,1449916_at,1449959_x_at,1449967_at,1449969_at,1450118_a_at,1450123_at,1450175_a_at,1450181_at,1450338_x_at,1450349_at,1450389_s_at,1450427_at,1450530_at,1450682_at,1450763_x_at,1450773_at,1450917_at,1451203_at,1451620_at,1451633_a_at,1451635_at,1451785_at,1451801_at,1451886_at,1452003_at,1452389_at,1452498_at,1452555_at,1452565_x_at,1452651_a_at,1453167_at,1453203_at,1453434_at,1453443_at,1453526_at,1453551_at,1453592_at,1453621_at,1453632_at,1453680_at,1453758_at,1453886_a_at,1454110_at,1454163_at,1454202_a_at,1454287_at,1454500_at,1454598_at,1454749_at,1455234_at,1455259_a_at,1455298_at,1455374_at,1455444_at,1455519_at,1455645_at,1455736_at,1455748_at,1455830_s_at,1455865_at,1455913_x_at,1456123_at,1456202_at,1456327_at,1456432_at,1456595_x_at,1456637_at,1456917_at,1456965_at,1456977_at,1456994_at,1457153_at,1457257_x_at,1457429_s_at,1457435_x_at,1457475_at,1457516_at,1457582_at,1457626_at,1457738_at,1457812_at,1457833_at,1457883_at,1457981_x_at,1458016_at,1458072_at,1458087_at,1458119_at,1458188_at,1458269_at,1458301_x_at,1458336_at,1458456_x_at,1458526_at,1458635_at,1458666_at,1458759_at,1458761_at,1458810_at,1458859_at,1458865_at,1458944_at,1459033_at,1459036_at,1459073_x_at,1459115_at,1459180_at,1459236_at,1459435_at,1459508_at,1459542_at,1459554_at,1459558_at,1459614_at,1459633_at,1459654_at,1459689_at,1459706_at,1459709_at,1459717_at,1459750_s_at,1459844_at,1459870_x_at,1460038_at,1460608_at GENE_SYMBOLS TNP1,CEACAM7,,TBR1,TNNI2,MMP13,TNNC2,NPY2R,CKM,PVALB,DHCR24,MYOT,RBFOX1,RIPK4,NRSN1,TNNT2,HAVCR1,AQP5,RHAG,SERPINB2,APOM,SMTNL1,MYF6,,ATP2A1,EHF,SEMA3E,,,,,,,,,,SYT2,TEX21P,SERPINA1,TEX43,MYF5,SCRG1,TAS1R3,SLN,PAX9,TRIM7,NR6A1,,CENPH,,CLEC2D,CYP1A1,USP17L2,HTR7,LENEP,,,SEMG1,TFF2,CASQ2,KRT6C,SH3BGR,EPHA1,NCAN,DGLUCY,C4orf19,SLC29A4,FCRL1,FOXN4,NCAM2,PSRC1,CHIA,OTC,MGAT5,COL4A4,,CABP7,TRDN,TRDN,TRDN,,MYH4,,TMED7,TTN,TTN,TRIM17,ADORA2A,MYH1,TRAT1,PRKCA,PTPRJ,SLC15A5,ACTA1,CFTR,DEFB4A,MYH1,,,ANKRD23,CKMT2,HEPACAM,CEP128,PRDM16,THEM5,,,BMAL2,SPACA7,CFAP206,,PROX2,HSPA4L,DAAM2,,,,LIPM,BCLAF1,PCDH10,LRP2BP,FAM131B,SPATA16,,CECR2,NPHP3,,,MEIOB,ODAD3,SEMA3B,,,HIF1A,,POT1,,,,,,,PAPPA,,,,,,,,,,,,UBE2Q2,RUFY2,A2M,RAD54B,CADM2,FOCAD,GRIA1,B3GALT6,NEB,MC1R,MYPN,UPK1B,GRIP1,TNR,MRAP2,,ITSN1,CORO6,NLRP4,ASCL1,KBTBD6,,DPY19L2,,,,OR5B3,GARIN3,UBE2U,,SKOR1,,,HAPLN1,,CTXN3,NPAS3,,,,MYOM2,ZSWIM5,KYAT1,RELCH,NXPH1,AK4,,SOCS2,,,SUSD5,TRIM63,OSBPL6,CHRNA9,,SERPINB5,NMBR,CLHC1,KCNK9,DDO,,,,,ZIC1,,KIAA0232,,,SLC25A41,,ASB15,,GRIK1,FARSA,COL12A1,ARPP21,C2orf80,,SNTG1,CPA6,,,NEXMIF,TRIM17,IKZF3,NAV2,,,,,,ANKRA2,,SMYD3,SMO,COA7,,,,,,,DLK1,,,,,,,,EYA1,MS4A2,,,RBM46,,,,,,,CD28,,,GABRB1,TRIM5,,ISL1,,,RSPH4A,,KLHL41,,,,,,,,,,,,,,,,,,PMS2,,,,LRRC39,FASTKD3,,,,,,ALS2,,,,,,USP53,,,,,,,,,,,,,FLRT2,,,,,,,,,FAM53A,,,,RLN1,ACTN2,MYL11,CRAT,PYGM,IL16,KCNK1,FABP1,PDLIM3,THBS4,TREH,GDPD3,,KCNH2,,CCDC7,PBX4,,SIM1,TMOD4,TNNT3,RYR2,,CUX2,,,PIP5K1B,CHRNA6,B3GALT1,FABP6,WNT3,KCND2,MYOM2,MB,,GNGT1,SLC22A25,RPGRIP1,TRDN,SPEG,RBM14,CD27,,,,MYL1,,PRPS1L1,,,,POLQ,LRRC39,THOC7,C1orf50,,CCDC34,SLC25A26,,,TEX33,,,,PCNT,B3GALT1,UTP23,ID4,KCNJ3,GABRA2,,MYBPC1,MYBPC2,DYNLT1,PRAMEF2,INSM1,TTR,SLC5A12,ELFN2,,,GH1,LRRTM2,,,,,,NECTIN3,SBSPON,MYOM2,,,,,,,,,,,ZNF729,STAC3,SLC25A27,,PCDH9,,,C3orf18,,METTL21EP,,,,,,,,,,,,,,,,,,,,,,,,ZIC5,SMIM17,ADGRA1,TNIP2,,POU3F1,CACNA1B FOUNDER_NAMES