Human Gene Set: LOPEZ_TRANSLATION_VIA_FN1_SIGNALING


Standard name LOPEZ_TRANSLATION_VIA_FN1_SIGNALING
Systematic name M2426
Brief description Genes translationally up-regulated in HUVEC cells (endothelium) grown on FN1 [GeneID=2335] compared to those grown on laminin 1.
Full description or abstract Integrin signaling promotes, through p21-activated kinase, phosphorylation and inactivation of the tumor suppressor merlin, thus removing a block to mitogenesis in normal cells. However, the biochemical function of merlin and the effector pathways critical for the pathogenesis of malignant mesothelioma and other NF2-related malignancies are not known. We report that integrin-specific signaling promotes activation of mTORC1 and cap-dependent mRNA translation. Depletion of merlin rescues mTORC1 signaling in cells deprived of anchorage to a permissive extracellular matrix, suggesting that integrin signaling controls mTORC1 through inactivation of merlin. This signaling pathway controls translation of the cyclin D1 mRNA and, thereby, cell cycle progression. In addition, it promotes cell survival. Analysis of a panel of malignant mesothelioma cell lines reveals a strong correlation between loss of merlin and activation of mTORC1. Merlin-negative lines are sensitive to the growth-inhibitory effect of rapamycin, and the expression of recombinant merlin renders them partially resistant to rapamycin. Conversely, depletion of merlin restores rapamycin sensitivity in merlin-positive lines. These results indicate that integrin-mediated adhesion promotes mTORC1 signaling through the inactivation of merlin. Furthermore, they reveal that merlin-negative mesotheliomas display unregulated mTORC1 signaling and are sensitive to rapamycin, thus providing a preclinical rationale for prospective, biomarker-driven clinical studies of mTORC1 inhibitors in these tumors.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 19451229   Authors: López-Lago MA,Okada T,Murillo MM,Socci N,Giancotti FG
Exact source Fig. 2D
Related gene sets (show 22 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
HUMAN_GENE_SYMBOL
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 35 genes
Gene families ? Categorize these 35 genes by gene family
Show members (show 36 source identifiers mapped to 35 genes)
Version history 3.1: First introduced

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