Human Gene Set: GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_UP

For the Mouse gene set with the same name, see GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_UP

Standard name GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_UP
Systematic name M1373
Brief description Genes up-regulated in MMH-RT cells (hepatocytes displaying an invasive, metastatic phenotype) during epithelial to mesenchymal transition (EMT).
Full description or abstract 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16607286   Authors: Gotzmann J,Fischer AN,Zojer M,Mikula M,Proell V,Huber H,Jechlinger M,Waerner T,Weith A,Beug H,Mikulits W
Exact source Fig 4, 5: red
Related gene sets (show 1 additional gene sets from the source publication)

(show 7 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform or
identifier namespace		 AFFY_Mu11K
Dataset references  
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 68 genes
Gene families ? Categorize these 68 genes by gene family
Show members (show 77 source identifiers mapped to 68 genes)
Version history 3.1: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.