TNC (tenascin C (hexabrachion))

2008-02-01   Martin Degen , Ruth Chiquet-Ehrismann 

Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland

Identity

HGNC
LOCATION
9q33.1
LOCUSID
ALIAS
150-225,DFNA56,GMEM,GP,HXB,JI,TN,TN-C
FUSION GENES

DNA/RNA

Atlas Image
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.

Proteins

Atlas Image
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 name
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 name
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.

Bibliography

Pubmed IDLast YearTitleAuthors
164613312006Vascular tenascin-C regulates cardiac endothelial phenotype and neovascularization.Ballard VL et al
63427601983Human glioma-mesenchymal extracellular matrix antigen defined by monoclonal antibody.Bourdon MA et al
62026991984Chick myotendinous antigen. II. A novel extracellular glycoprotein complex consisting of large disulfide-linked subunits.Chiquet M et al
128456162003Tenascins: regulation and putative functions during pathological stress.Chiquet-Ehrismann R et al
108423552000The tenascin family of ECM glycoproteins: structure, function, and regulation during embryonic development and tissue remodeling.Jones FS et al
161158192005Coding SNP in tenascin-C Fn-III-D domain associates with adult asthma.Matsuda A et al
160494802005Genes that mediate breast cancer metastasis to lung.Minn AJ et al
166321942006Tenascin-C induced signaling in cancer.Orend G et al
157436792005Potential oncogenic action of tenascin-C in tumorigenesis.Orend G et al
75389741995Tenascin-C in serum: a questionable tumor marker.Schenk S et al
181855802008Endogenous human microRNAs that suppress breast cancer metastasis.Tavazoie SF et al
85487611996Tenascin-C expression by angiogenic vessels in human astrocytomas and by human brain endothelial cells in vitro.Zagzag D et al

Other Information

Locus ID:

NCBI: 3371
MIM: 187380
HGNC: 5318
Ensembl: ENSG00000041982

Variants:

dbSNP: 3371
ClinVar: 3371
TCGA: ENSG00000041982
COSMIC: TNC

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000041982ENST00000341037J3QSU6
ENSG00000041982ENST00000350763P24821
ENSG00000041982ENST00000423613E9PC84
ENSG00000041982ENST00000534839F5H5D6
ENSG00000041982ENST00000535648F5H7V9
ENSG00000041982ENST00000537320P24821
ENSG00000041982ENST00000542877F5H7V9
ENSG00000041982ENST00000544972H0YGZ3
ENSG00000041982ENST00000635336A0A0U1RR80

Expression (GTEx)

0
50
100
150
200
250
300
350
400

Pathways

PathwaySourceExternal ID
Focal adhesionKEGGko04510
ECM-receptor interactionKEGGko04512
Focal adhesionKEGGhsa04510
ECM-receptor interactionKEGGhsa04512
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206
Extracellular matrix organizationREACTOMER-HSA-1474244
Non-integrin membrane-ECM interactionsREACTOMER-HSA-3000171
Syndecan interactionsREACTOMER-HSA-3000170
ECM proteoglycansREACTOMER-HSA-3000178
Integrin cell surface interactionsREACTOMER-HSA-216083

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
195616172009Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease.219
150599782004Tenascin-C and SF/HGF produced by myofibroblasts in vitro provide convergent pro-invasive signals to human colon cancer cells through RhoA and Rac.109
198874512010Incorporation of tenascin-C into the extracellular matrix by periostin underlies an extracellular meshwork architecture.83
175848332007Myofibre damage in human skeletal muscle: effects of electrical stimulation versus voluntary contraction.62
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
215012932011Osteopontin, intrinsic tissue regulator of intractable inflammatory diseases.59
191475582009Tenascin-C is a novel RBPJkappa-induced target gene for Notch signaling in gliomas.52
194059592009Tumour-associated tenascin-C isoforms promote breast cancer cell invasion and growth by matrix metalloproteinase-dependent and independent mechanisms.52
201071852010Transcriptional regulation of the endogenous danger signal tenascin-C: a novel autocrine loop in inflammation.50
272567162016Tenascin-C drives persistence of organ fibrosis.45

Citation

Martin Degen ; Ruth Chiquet-Ehrismann

TNC (tenascin C (hexabrachion))

Atlas Genet Cytogenet Oncol Haematol. 2008-02-01

Online version: http://atlasgeneticsoncology.org/gene/42597/tnc-(tenascin-c-(hexabrachion))