Gene Set: SASAI_TARGETS_OF_CXCR6_AND_PTCH1_UP

Standard name SASAI_TARGETS_OF_CXCR6_AND_PTCH1_UP
Systematic name M10694
Brief description Up-regulated genes in medulloblastoma tumors from heterozygotic CXCR6 [GeneID=10663] knockout mice compared to those from PTCH1 [GeneID=5727] heterozygotic knockout mice.
Full description or abstract The sonic hedgehog (Shh) pathway is activated in approximately 30% of human medulloblastoma resulting in increased expression of downstream target genes. In about half of these cases, this has been shown to be a consequence of mutations in regulatory genes within the pathway, including Ptc1, Smo, and Sufu. However, for some tumors, no mutations have been detected in known pathway genes. This suggests that either mutations in other genes promote tumorigenesis or that epigenetic alterations increase pathway activity in these tumors. Here, we report that 3% to 4% of mice lacking either one or both functional copies of Cxcr6 develop medulloblastoma. Although CXCR6 is not known to be involved in Shh signaling, tumors derived from Cxcr6 mutant mice expressed Shh pathway target genes including Gli1, Gli2, Ptc2, and Sfrp1, indicating elevated pathway activity. Interestingly, the level of Ptc1 expression was decreased in tumor cells although two normal copies of Ptc1 were retained. This implies that reduced CXCR6 function leads to suppression of Ptc1 thereby increasing Smoothened function and promoting tumorigenesis. We used a direct transplant model to test the sensitivity of medulloblastoma arising in Cxcr6 mutant mice to a small-molecule inhibitor of Smoothened (HhAntag). We found that transplanted tumors were dramatically inhibited in mice treated for only 4 days with HhAntag. These findings suggest that HhAntag may be effective against tumors lacking mutations in known Shh pathway genes.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17413002   Authors: Sasai K,Romer JT,Kimura H,Eberhart DE,Rice DS,Curran T
Exact source Table 2S: log-ratio > 0
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
Organism Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform AFFY_Mouse430
Dataset references (show 1 datasets)
Download gene set format: grp | text | gmt | gmx | xml
Compute overlaps (show collections to investigate for overlap with this gene set)
Compendia expression profiles GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 14 genes
Gene families Categorize these 14 genes by gene family
Show members (show 19 members mapped to 14 genes)
Version history 3.0: First introduced

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