Systematic name M19048
Brief description Genes down-regulated in T98G cells (glioblastoma) by TNC [GeneID=3371].
Full description or abstract Tenascin-C is an adhesion-modulating extracellular matrix molecule that is highly expressed in tumor stroma and stimulates tumor cell proliferation. Adhesion of T98G glioblastoma cells to a fibronectin substratum is inhibited by tenascin-C. To address the mechanism of action, we performed a RNA expression analysis of T89G cells grown in the presence or absence of tenascin-C and found that tenascin-C down-regulates tropomyosin-1. Upon overexpression of tropomyosin-1, cell spreading on a fibronectin/tenascin-C substratum was restored, indicating that tenascin-C destabilizes actin stress fibers through down-regulation of tropomyosin-1. Tenascin-C also increased the expression of the endothelin receptor type A and stimulated the corresponding mitogen-activated protein kinase signaling pathway, which triggers extracellular signal-regulated kinase 1/2 phosphorylation and c-Fos expression. Tenascin-C additionally caused down-regulation of the Wnt inhibitor Dickkopf 1. In consequence, Wnt signaling was enhanced through stabilization of beta-catenin and stimulated the expression of the beta-catenin target Id2. Finally, our in vivo data derived from astrocytoma tissue arrays link increased tenascin-C and Id2 expression with high malignancy. Because increased endothelin and Wnt signaling, as well as reduced tropomyosin-1 expression, are closely linked to transformation and tumorigenesis, we suggest that tenascin-C specifically modulates these signaling pathways to enhance proliferation of glioma cells.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 15492259   Authors: Ruiz C,Huang W,Hegi ME,Lange K,Hamou MF,Fluri E,Oakeley EJ,Chiquet-Ehrismann R,Orend G
Exact source Table 1S: Fold Decrease < 0
Related gene sets (show 1 additional gene sets from the source publication)

(show 1 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
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 143 genes
Gene families ? Categorize these 143 genes by gene family
Show members (show 182 source identifiers mapped to 143 genes)
Version history  

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