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TNC (tenascin C (hexabrachion))

Identity

Other namesCytotactin
GMEM
GP (150-225)
Glioma associated extracellular matrix antigen
Hexabrachion
J1
Myotendinous antigen
Neuronectin
TN
HGNC (Hugo) TNC
LocusID (NCBI) 3371
Location 9q33.1
Location_base_pair Starts at 117781854 and ends at 117880536 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

 
  Table shows the lengths of the exons and introns of human tenascin-C.
Description The tenascin-C gene consists of 27 exons spanning 97.63 kb of genomic DNA.
Transcription 7271 bp mRNA transcribed on the reverse strand; 6333 bp open reading frame.
The transcript starts with a non-coding exon 1 (179 bp) followed by exon 2, which contains the start codon (ATG) for translation initiation. Exon 1 is located 26827 bp upstream of exon 2.

Protein

 
  Schematic representation of a monomeric tenascin-C subunit.
Description Tenascin-C consists of structural motifs arranged in a linear order. Mammalian tenascin-C proteins contain amino-terminal heptad repeats, 14.5 EGF-like repeats, 8 constant FN III domains, whereas 9 additional FN III domains can be included in a combinatorial manner by alternative splicing, and a carboxyl-terminal fibrinogen globe. A prominent feature of tenascin-C is the assembly into hexamers, so-called hexabrachions.
The primary sequence encodes a protein of 2110 amino acids. Amino acids 1-22 represent the secretion signal, amino acids 189-621 constitute the EGF-like repeats, and amino acids 622-1882 account for the FNIII domains. SDS-Page analysis revealed a molecular weight of full-length tenascin-C of 250kDa - 300kDa per subunit under reducing conditions.
Alternative splicing within the stretch of FN III domains results in a great number and diversity in tenascin-C isoforms.
Expression More than two decades ago, tenascin-C was discovered as an extracellular matrix protein (ECM) enriched in the stroma of gliomas and as a myotendinous antigen. Tenascin-C expression is highly regulated both during development and in the adult. Tenascin-C levels are high during embryogenesis, but almost absent during normal postnatal life with some basal expression detectable in tendons and ligaments only. In adult life, tenascin-C is also expressed within the sub-ventricular zone in the central nervous system, a region that constitutes the neural stem cell niche. A prominent feature of tenascin-C is its re-appearance in response to pathological situations such as infection, inflammation and tissue remodeling. Another striking example of a pathological situation leading to the re-expression of tenascin-C is the onset of tumorigenesis, where tenascin-C is specifically expressed in the activated tumor stroma. Tenascin-C can be induced by various stimuli, such as the pro- and anti-inflammatory cytokines, interleukins, TNFa or IFNg and growth factors such as TGFb , EGF or PDGF. Furthermore, tenascin-C inducing stimuli include mechanical stress, hypoxia, and reactive oxygen species, factors or conditions which also might play a prominent role in tumors.
Localisation Extracellular matrix.
Function Adhesion: Tenascin-C acts as an anti-adhesive substratum for a large variety of cells. Active inhibition of cell spreading was further confirmed by mixing tenascin-C together with fibronectin, which is a classical adhesion protein. Whereas cells on fibronectin nicely spread, form focal contacts and actin stress fibers, the same cells plated on a mixed fibronectin-tenascin-C substratum are not able to spread and do not form focal contacts and actin cables.
Migration: Tenascin-C enhances migration and invasiveness of different cancer cells.
Proliferation: Tenascin-C stimulates cancer cell proliferation.
Angiogenesis: Tenascin-C is expressed around angiogenic vessels in many tumors and there is evidence that it promotes and regulates angiogenesis in vitro and in vivo. Moreover, in glioma patients, clinical studies revealed an inhibition of tumor angiogenesis by applying antibodies directed against tenascin-C.
Homology Tenascin-C belongs to the tenascin family, which is a highly conserved family of large oligomeric extracellular matrix proteins. Vertebrate genomes harbor four tenascin genes, which have been termed tenascin-C, tenascin-XB (TNXB), tenascin-R, and tenascin-W.

Mutations

Germinal A SNP was identified resulting in an amino acid substitution (Leu1677Ile in the tenascin-C FN III domain D) which strongly associates with adult bronchial asthma. Therefore, this SNP might be an asthma marker and may be important in its pathogenesis.

Implicated in

Entity Cancer (general)
Oncogenesis Tenascin-C is strongly expressed in the stroma of various cancers and has been reported to be associated with the invasive front of tumors. For cancers in the lung, colon, and brain, high tenascin-C expression correlates with poor prognosis, whereas in other cancers no clear correlation between tenascin-C and survival or malignancy exists. In search for new diagnostic or prognostic tumor markers, tenascin-C levels have often been analyzed in sera of cancer patients and its potential value as a biomarker has been evaluated. Although elevated tenascin-C serum levels have been found in certain cancers, it still remains a questionable tumor marker. Tenascin-C levels are scattered over a wide range with many cancer patients having normal tenascin-C concentrations and its expression strongly correlates with inflammation or infection.
  
Entity Breast cancer
Oncogenesis By means of in vivo selection and microarray analysis a gene expression signature was identified that mediates breast cancer metastasis to lung. Tenascin-C is one of those genes that have been found to belong to the lung metastasis signature genes.
A recent study identified tenascin-C as a direct target gene for the microRNA miR-335. This microRNA is specifically lost as human breast cancer cells develop metastatic potential. Knockdown of tenascin-C in the highly metastatic LM2 cells (a metastatic derivative of the human breast cancer cell line MDA-MB-231) reduced migration in a trans-well assay and significantly inhibited lung colonization by LM2 cells.
  

External links

Nomenclature
HGNC (Hugo)TNC   5318
Cards
AtlasTNCID42597ch9q33
Entrez_Gene (NCBI)TNC  3371  tenascin C
GeneCards (Weizmann)TNC
Ensembl (Hinxton)ENSG00000041982 [Gene_View]  chr9:117781854-117880536 [Contig_View]  TNC [Vega]
ICGC DataPortalENSG00000041982
AceView (NCBI)TNC
Genatlas (Paris)TNC
WikiGenes3371
SOURCE (Princeton)NM_002160
Genomic and cartography
GoldenPath (UCSC)TNC  -  9q33.1   chr9:117781854-117880536 -  9q32-q34   [Description]    (hg19-Feb_2009)
EnsemblTNC - 9q32-q34 [CytoView]
Mapping of homologs : NCBITNC [Mapview]
OMIM187380   615629   
Gene and transcription
Genbank (Entrez)AB210038 AI266750 AI964017 AK304015 BC151843
RefSeq transcript (Entrez)NM_002160
RefSeq genomic (Entrez)AC_000141 NC_000009 NC_018920 NG_029637 NT_008470 NW_001839236 NW_004929366
Consensus coding sequences : CCDS (NCBI)TNC
Cluster EST : UnigeneHs.734766 [ NCBI ]
CGAP (NCI)Hs.734766
Alternative Splicing : Fast-db (Paris)GSHG0031098
Alternative Splicing GalleryENSG00000041982
Gene ExpressionTNC [ NCBI-GEO ]     TNC [ SEEK ]   TNC [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP24821 (Uniprot)
NextProtP24821  [Medical]
With graphics : InterProP24821
Splice isoforms : SwissVarP24821 (Swissvar)
Domaine pattern : Prosite (Expaxy)EGF_1 (PS00022)    EGF_2 (PS01186)    EGF_3 (PS50026)    FIBRINOGEN_C_2 (PS51406)    FN3 (PS50853)   
Domains : Interpro (EBI)EG-like_dom    EGF-like_CS    EGF_extracell    Fibrinogen_a/b/g_C_1    Fibrinogen_a/b/g_C_2    Fibrinogen_a/b/g_C_dom    Fibronectin_type3    Ig-like_fold   
Related proteins : CluSTrP24821
Domain families : Pfam (Sanger)EGF_2 (PF07974)    Fibrinogen_C (PF00147)    fn3 (PF00041)    hEGF (PF12661)   
Domain families : Pfam (NCBI)pfam07974    pfam00147    pfam00041    pfam12661   
Domain families : Smart (EMBL)EGF (SM00181)  FBG (SM00186)  FN3 (SM00060)  
DMDM Disease mutations3371
Blocks (Seattle)P24821
PDB (SRS)1TEN    2RB8    2RBL   
PDB (PDBSum)1TEN    2RB8    2RBL   
PDB (IMB)1TEN    2RB8    2RBL   
PDB (RSDB)1TEN    2RB8    2RBL   
Human Protein AtlasENSG00000041982
Peptide AtlasP24821
HPRD01756
IPIIPI00031008   IPI00220211   IPI01015608   IPI00220213   IPI00220214   IPI00220216   IPI00908788   IPI00220212   IPI00747950   IPI00867560   IPI01011141   IPI01014388   
Protein Interaction databases
DIP (DOE-UCLA)P24821
IntAct (EBI)P24821
FunCoupENSG00000041982
BioGRIDTNC
IntegromeDBTNC
STRING (EMBL)TNC
Ontologies - Pathways
QuickGOP24821
Ontology : AmiGOosteoblast differentiation  extracellular region  basement membrane  interstitial matrix  extracellular space  cell adhesion  negative regulation of cell adhesion  neuromuscular junction development  positive regulation of cell proliferation  response to wounding  response to mechanical stimulus  positive regulation of gene expression  peripheral nervous system axon regeneration  membrane  extracellular matrix organization  extracellular matrix  extracellular matrix  wound healing  odontogenesis of dentin-containing tooth  response to ethanol  syndecan binding  bud outgrowth involved in lung branching  mesenchymal-epithelial cell signaling involved in prostate gland development  prostate gland epithelium morphogenesis  cellular response to retinoic acid  cellular response to vitamin D  response to fibroblast growth factor  cellular response to prostaglandin D stimulus  
Ontology : EGO-EBIosteoblast differentiation  extracellular region  basement membrane  interstitial matrix  extracellular space  cell adhesion  negative regulation of cell adhesion  neuromuscular junction development  positive regulation of cell proliferation  response to wounding  response to mechanical stimulus  positive regulation of gene expression  peripheral nervous system axon regeneration  membrane  extracellular matrix organization  extracellular matrix  extracellular matrix  wound healing  odontogenesis of dentin-containing tooth  response to ethanol  syndecan binding  bud outgrowth involved in lung branching  mesenchymal-epithelial cell signaling involved in prostate gland development  prostate gland epithelium morphogenesis  cellular response to retinoic acid  cellular response to vitamin D  response to fibroblast growth factor  cellular response to prostaglandin D stimulus  
Pathways : KEGGPI3K-Akt signaling pathway    Focal adhesion    ECM-receptor interaction    MicroRNAs in cancer   
REACTOMEP24821 [protein]
REACTOME PathwaysREACT_118779 Extracellular matrix organization [pathway]
Protein Interaction DatabaseTNC
Wikipedia pathwaysTNC
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)TNC
SNP (GeneSNP Utah)TNC
SNP : HGBaseTNC
Genetic variants : HAPMAPTNC
1000_GenomesTNC 
ICGC programENSG00000041982 
CONAN: Copy Number AnalysisTNC 
Somatic Mutations in Cancer : COSMICTNC 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
DECIPHER (Syndromes)9:117781854-117880536
Mutations and Diseases : HGMDTNC
OMIM187380    615629   
MedgenTNC
GENETestsTNC
Disease Genetic AssociationTNC
Huge Navigator TNC [HugePedia]  TNC [HugeCancerGEM]
Genomic VariantsTNC  TNC [DGVbeta]
Exome VariantTNC
dbVarTNC
ClinVarTNC
snp3D : Map Gene to Disease3371
DGIdb (Curated mutations)TNC
DGIdb (Drug Gene Interaction db)TNC
General knowledge
Homologs : HomoloGeneTNC
Homology/Alignments : Family Browser (UCSC)TNC
Phylogenetic Trees/Animal Genes : TreeFamTNC
Chemical/Protein Interactions : CTD3371
Chemical/Pharm GKB GenePA35103
Clinical trialTNC
Cancer Resource (Charite)ENSG00000041982
Other databases
Probes
Litterature
PubMed179 Pubmed reference(s) in Entrez
CoreMineTNC
GoPubMedTNC
iHOPTNC

Bibliography

Human glioma-mesenchymal extracellular matrix antigen defined by monoclonal antibody.
Bourdon MA, Wikstrand CJ, Furthmayr H, Matthews TJ, Bigner DD.
Cancer Res. 1983 Jun;43(6):2796-805.
PMID 6342760
 
Chick myotendinous antigen II. A novel extracellular glycoprotein complex consisting of large disulfide-linked subunits.
Chiquet M, Fambrough DM.
J Cell Biol. 1984 Jun;98(6):1937-46.
PMID 6202699
 
Tenascin interferes with fibronectin action.
Chiquet-Ehrismann R, Kalla P, Pearson CA, Beck K, Chiquet M.
Cell. 1988 May 6;53(3):383-90.
PMID 2452695
 
Tenascin-C in serum: a questionable tumor marker.
Schenk S, Muser J, Vollmer G, Chiquet-Ehrismann R.
Int J Cancer. 1995 May 16;61(4):443-9.
PMID 7538974
 
Tenascin-C expression by angiogenic vessels in human astrocytomas and by human brain endothelial cells in vitro.
Zagzag D, Friedlander DR, Dosik J, et al.
Cancer Res. 1996 Jan 1;56(1):182-9.
PMID 8548761
 
The Tenascin family of ECM Glycoproteins: Structure, Function, and Regulation Durig Embryonic Development and Tissue Remodeling.
Jones FS and Jones PL.
Dev Dyn. 2000 Jun;218(2):235-59. (REVIEW)
PMID 10842355
 
Tenascins: regulation and putative functions during pathological stress.
Chiquet-Ehrismann R, Chiquet M.
J Pathol. 2003 Jul;200(4):488-99. (REVIEW)
PMID 12845616
 
Coding SNP in tenascin-C Fn-III-D domain associates with adult asthma.
Matsuda A, Hirota T, Akahoshi M, et al.
Human Molecular Genetics. 2005 Oct 1;14(19):2779-86.
PMID 16115819
 
Genes that mediate breast cancer metastasis to lung.
Minn A, Gupta GP, Siegel PM, et al.
Nature. 2005 Jul 28;436(7050):518-24.
PMID 16049480
 
Potential oncogenic action of tenascin-C in tumorigenesis.
Orend G.
Int J Biochem Cell Biol. 2005 May;37(5):1066-83. (REVIEW)
PMID 15743679
 
Vascular tenascin-C regulates cardiac endothelial phenotype and neovascularization.
Ballard VL, Sharma A, Duignan I, et al.
Faseb J. 2006 Apr;20(6):717-9.
PMID 16461331
 
Tenascin-C induced signaling in cancer.
Orend G and Chiquet-Ehrismann R.
Cancer Lett. 2006 Dec 8;244(2):143-63. (REVIEW)
PMID 16632194
 
Endogenous human microRNAs that suppress breast cancer metastasis.
Tavazoie SF, Alarcon C, Oskarsson T, et al.
Nature. 2008 Jan 10;451(7175):147-52.
PMID 18185580
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written02-2008Martin Degen, Ruth Chiquet-Ehrismann
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland

Citation

This paper should be referenced as such :
Degen, M ; Chiquet-Ehrismann, R
TNC (tenascin C (hexabrachion))
Atlas Genet Cytogenet Oncol Haematol. 2008;12(6):446-448.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/TNCID42597ch9q33.html

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indexed on : Thu Dec 4 15:24:22 CET 2014

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