Gene Set: HOELZEL_NF1_TARGETS_DN

Standard name HOELZEL_NF1_TARGETS_DN
Systematic name M2143
Brief description Genes down-regulated in SH-SY5Y cells (neuroblastoma) after knockdown of NF1 [GeneID=4763] by RNAi.
Full description or abstract Retinoic acid (RA) induces differentiation of neuroblastoma cells in vitro and is used with variable success to treat aggressive forms of this disease. This variability in clinical response to RA is enigmatic, as no mutations in components of the RA signaling cascade have been found. Using a large-scale RNAi genetic screen, we identify crosstalk between the tumor suppressor NF1 and retinoic acid-induced differentiation in neuroblastoma. Loss of NF1 activates RAS-MEK signaling, which in turn represses ZNF423, a critical transcriptional coactivator of the retinoic acid receptors. Neuroblastomas with low levels of both NF1 and ZNF423 have extremely poor outcome. We find NF1 mutations in neuroblastoma cell lines and in primary tumors. Inhibition of MEK signaling downstream of NF1 restores responsiveness to RA, suggesting a therapeutic strategy to overcome RA resistance in NF1-deficient neuroblastomas.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 20655465   Authors: Hölzel M,Huang S,Koster J,Ora I,Lakeman A,Caron H,Nijkamp W,Xie J,Callens T,Asgharzadeh S,Seeger RC,Messiaen L,Versteeg R,Bernards R
Exact source Table 1S: Log Ratio (vs pRS) < 0
Related gene sets (show 1 additional gene sets from the source publication)

(show 31 gene sets from the same authors)
External links  
Filtered by similarity
Organism Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform AFFY_HG_U133
Dataset references  
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 117 genes
Gene families Categorize these 117 genes by gene family
Show members (show 167 members mapped to 117 genes)
Version history 3.1: First introduced

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