STANDARD_NAME	GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_UP
SYSTEMATIC_NAME	M1373
COLLECTION	C2:CGP
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_UP
NAMESPACE	AFFY_Mu11K
DESCRIPTION_BRIEF	Genes up-regulated in MMH-RT cells (hepatocytes displaying an invasive, metastatic phenotype) during epithelial to mesenchymal transition (EMT).
DESCRIPTION_FULL	Polarized hepatocytes expressing hyperactive Ha-Ras adopt an invasive and metastatic phenotype in cooperation with transforming growth factor (TGF)-beta. This dramatic increase in malignancy is displayed by an epithelial to mesenchymal transition (EMT), which mimics the TGF-beta-mediated progression of human hepatocellular carcinomas. In culture, hepatocellular EMT occurs highly synchronously, facilitating the analysis of molecular events underlying the various stages of this process. Here, we show that in response to TGF-beta, phosphorylated Smads rapidly translocated into the nucleus and activated transcription of target genes such as E-cadherin repressors of the Snail superfamily, causing loss of cell adhesion. Within the TGF-beta superfamily of cytokines, TGF-beta1, -beta2 and -beta3 were specific for the induction of hepatocellular EMT. Expression profiling of EMT kinetics revealed 78 up- and 235 downregulated genes, which preferentially modulate metabolic activities, extracellular matrix composition, transcriptional activities and cell survival. Independent of the genetic background, platelet-derived growth factor (PDGF)-A ligand and both PDGF receptor subunits were highly elevated, together with autocrine secretion of bioactive PDGF. Interference with PDGF signalling by employing hepatocytes expressing the dominant-negative PDGF-alpha receptor revealed decreased TGF-beta-induced migration in vitro and efficient suppression of tumour growth in vivo. In conclusion, these results provide evidence for a crucial role of PDGF in TGF-beta-mediated tumour progression of hepatocytes and suggest PDGF as a target for therapeutic intervention in liver cancer.
PMID	16607286
GEOID	
AUTHORS	Gotzmann J,Fischer AN,Zojer M,Mikula M,Proell V,Huber H,Jechlinger M,Waerner T,Weith A,Beug H,Mikulits W
CONTRIBUTOR	Jessica Robertson
CONTRIBUTOR_ORG	MSigDB Team
EXACT_SOURCE	Fig 4, 5: red
FILTERED_BY_SIMILARITY	
EXTERNAL_NAMES_FOR_SIMILAR_TERMS	
EXTERNAL_DETAILS_URL	
SOURCE_MEMBERS	AB000096_at,AF000168_at,AF012709_s_at,AF016583_at,d10061_s_at,d17546_s_at,D49544_s_at,d70842_s_at,d83596_s_at,ET62477_s_at,ET62820_s_at,j02870_s_at,j04694_s_at,j04695_s_at,l08235_s_at,l26489_s_at,L27439_s_at,l29479_s_at,l75822_s_at,M14757_s_at,m18184_s_at,M18194_f_at,m19681_s_at,m21952_s_at,m27960_s_at,M29464_s_at,m31131_s_at,m32309_s_at,M32484_s_at,M32745_s_at,M33960_s_at,m70642_s_at,M72394_s_at,M72414_s_at,M74227_s_at,m95604_s_at,Msa.2173.0_at,Msa.2254.0_f_at,Msa.397.0_at,Msa.497.0_s_at,Msa.544.0_s_at,Msa.547.0_f_at,s64539_s_at,u03283_s_at,u08020_f_at,U19119_s_at,U19271_s_at,u27177_s_at,u28789_s_at,u33840_s_at,u36475_s_at,u66620_s_at,u74359_s_at,u95116_at,v00755_s_at,x06086_f_at,x12761_s_at,X13297_s_at,X15591_s_at,x52046_s_at,X54149_s_at,x56304_s_at,X62154_s_at,X64837_s_at,X69620_s_at,x74134_s_at,X75285_s_at,X81323_s_at,X82786_s_at,X84037_s_at,Y00051_at,y00769_s_at,Y07941_s_at,z11997_s_at,z12297_s_at,z30970_s_at,Z31557_s_at
GENE_SYMBOLS	GATA2,MPDZ,CENPA,CHEK1,KIFC1,,,PROS1,ABCB1,FN1,PDGFA,,TGFB3,SERPINE1,PLA2G4A,MAP4,PPIC,INHBA,DCK,CHRNB1,,COL5A2,CTSV,IRGM,,ACTA2,,GADD45B,MCM3,OAT,INHBB,FBLN2,TPP2,MKI67,GLG1,NCAM1,PKP1,CCT6A,TOP1,COL18A1,EDN1,TEAD2,RPSA,COL4A1,COL4A2,CLU,FURIN,PLK4,IGFBP7,,CCL2,CSF1,IL4R,CDH2,ZFX,CCN2,SNAI1,ODC1,CYP1B1,COL1A1,RBL1,RBBP6,TRAF3,BRCA1,SMARCD1,SMAD1,PAFAH1B1,TIMP1,CTSV,JUN,COL3A1,TNC,NR2F1,ITGB1,HMGB1,CCL7,TIMP3
FOUNDER_NAMES