Human Gene Set: KOKKINAKIS_METHIONINE_DEPRIVATION_96HR_DN


Standard name KOKKINAKIS_METHIONINE_DEPRIVATION_96HR_DN
Systematic name M170
Brief description Genes down-regulated in MEWO cells (melanoma) after 96 h of methionine [PubChem=876] deprivation.
Full description or abstract Methionine deprivation stress (MDS) eliminates mitotic activity in melanoma cells regardless of stage, grade, or TP53 status, whereas it has a negligible effect on normal skin fibroblasts. In most cases, apoptosis accounts for the elimination of up to 90% of tumor cells from the culture within 72 hours after MDS, leaving a scattered population of multinucleated resistant cells. Loss of mitosis in tumor cells is associated with marked reduction of cyclin-dependent kinase (CDK) 1 transcription and/or loss of its active form (CDK1-P-Thr(161)), which is coincident with up-regulation of CDKN1A, CDKN1B, and CDKN1C (p21, p27, and p57). Expression of the proapoptotic LITAF, IFNGR, EREG, TNFSF/TNFRSF10 and TNFRSF12, FAS, and RNASEL is primarily up-regulated/induced in cells destined to undergo apoptosis. Loss of Aurora kinase B and BIRC5, which are required for histone H3 phosphorylation, is associated with the accumulation of surviving multinucleated cells. Nevertheless, noncycling survivors of MDS are sensitized to temozolomide, carmustin, and cisplatin to a much greater extent than normal skin fibroblasts possibly because of the suppression of MGMT/TOP1/POLB, MGMT/RAD52/RAD54, and cMET/RADD52, respectively. Sensitivity to these and additional genotoxic agents and radiation may also be acquired due to loss of cMET/OGG1, reduced glutathione reductase levels, and a G(2)-phase block that is a crucial step in the damage response associated with enhancement of drug toxicity. Although the genes controlling mitotic arrest and/or apoptosis in response to low extracellular methionine levels are unknown, it is likely that such control is exerted via the induction/up-regulation of tumor suppressors/growth inhibitor genes, such as TGFB, PTEN, GAS1, EGR3, BTG3, MDA7, and the proteoglycans (LUM, BGN, and DCN), as well as the down-regulation/loss of function of prosurvival genes, such as NFkappaB, MYC, and ERBB2. Although MDS targets several common genes in tumors, mutational variability among melanomas may decide which metabolic and signal transduction pathways will be activated or shutdown.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16908595   Authors: Kokkinakis DM,Brickner AG,Kirkwood JM,Liu X,Goldwasser JE,Kastrama A,Sander C,Bocangel D,Chada S
Exact source Table 1S: H/M 96h < 1
Related gene sets (show 3 additional gene sets from the source publication)

(show 53 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
Source platform or
identifier namespace		 AFFY_HG_U133
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 72 genes
Gene families ? Categorize these 72 genes by gene family
Show members (show 80 source identifiers mapped to 72 genes)
Version history 3.0: First introduced

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