Gene Set: YAUCH_HEDGEHOG_SIGNALING_PARACRINE_UP

Standard name YAUCH_HEDGEHOG_SIGNALING_PARACRINE_UP
Systematic name M19384
Brief description Genes up-regulated in mouse stroma of pancreatic adenocarcinoma zenografts after treatment with HhAntag, a hedgehog (Hh) pathway inhibitor.
Full description or abstract 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18754008   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
Exact source Supplmentary File 2: pvalue<0.05 and log2(Fold Change) > 1.5
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(show 3 gene sets from the same authors)
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Organism Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform AFFY_Mouse430
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