Malignant peripheral nerve sheath tumors (MPNST) are rare soft tissue sarcomas that are a major source of mortality in neurofibromatosis type 1 (NF1) patients. To identify MPNST driver genes, we performed a lentiviral short hairpin (sh) RNA screen, targeting all 130 genes up-regulated in neurofibroma and MPNSTs versus normal human nerve Schwann cells. NF1 mutant cells show activation of RAS/MAPK signaling, so a counter-screen in RAS mutant carcinoma cells was performed to exclude common RAS-pathway driven genes. We identified 7 genes specific for survival of MPSNT cells, including MEIS1. MEIS1 was frequently amplified or hypomethylated in human MPSNTs, correlating with elevated MEIS1 gene expression. In MPNST cells and in a genetically engineered mouse model, MEIS1 expression in developing nerve glial cells was necessary for MPNST growth. Mechanistically, MEIS1 drives MPNST cell growth via the transcription factor ID1, thereby suppressing expression of the cell cycle inhibitor p27(Kip) and maintaining cell survival.
Pubmed ID: 27333032 RIS Download
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View all literature mentionsPrivately held company that develops and produces antibodies, ELISA kits, ChIP kits, proteomic kits, and other related reagents used to study cell signaling pathways that impact human health.
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View all literature mentionsThis unknown targets Cyclin
View all literature mentionsThis monoclonal targets Id1
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View all literature mentionsThis polyclonal targets Human MEIS1
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View all literature mentionsMus musculus with name B6.129-Cdkn2atm1Rdp/Nci from IMSR.
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View all literature mentionsThis polyclonal targets Cleaved PARP (Asp214) (Human Specific)
View all literature mentionsCell line T265 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets Human MEIS1
View all literature mentionsThis polyclonal targets S100 isolated from cow brain.
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis polyclonal targets Phospho-Rb (Ser795)
View all literature mentionsCell line STS-26T is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Cdkn1b
View all literature mentionsThis polyclonal targets Human MEIS1
View all literature mentionsCell line S462 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line ST88-14 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis unknown targets Cyclin
View all literature mentionsThis monoclonal targets Id1
View all literature mentionsThis monoclonal targets Phospho-Rb (Ser807/811) (D20B12) XP Rabbit mAb
View all literature mentionsMus musculus with name B6.129-Cdkn2atm1Rdp/Nci from IMSR.
View all literature mentionsMus musculus with name B6.129-Cdkn2atm1Rdp/Nci from IMSR.
View all literature mentionsThis polyclonal targets Human MEIS1
View all literature mentionsThis polyclonal targets S100 isolated from cow brain.
View all literature mentionsThis monoclonal targets beta-Actin
View all literature mentionsThis polyclonal targets IgG
View all literature mentionsThis polyclonal targets Phospho-Rb (Ser795)
View all literature mentionsCell line S462 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line ST88-14 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line STS-26T is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis monoclonal targets Cdkn1b
View all literature mentionsThis polyclonal targets Cleaved PARP (Asp214) (Human Specific)
View all literature mentionsThis polyclonal targets Human MEIS1
View all literature mentionsThis polyclonal secondary targets IgG
View all literature mentionsThis unknown targets Cyclin
View all literature mentionsThis monoclonal targets Id1
View all literature mentionsThis monoclonal targets Phospho-Rb (Ser807/811) (D20B12) XP Rabbit mAb
View all literature mentions