TNN (tenascin N)

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

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

Identity

HGNC
LOCATION
1q25.1
LOCUSID
ALIAS
TN-W,TNW
FUSION GENES

DNA/RNA

Atlas Image
The distribution of the 19 exons is shown in the upper part, whereas the lengths of exons and introns are indicated in the lower part.

Description

The tenascin-W gene consists of 19 exons spanning 80.21 kb of genomic DNA.

Transcription

5005 bp mRNA transcribed in centromeric to telomeric orientation on the forward strand; 3885 bp open reading frame.
The transcript starts with a non-coding exon followed by exon 2, which contains the start codon (ATG) for translation initiation. Exon 1 is located 9448 bp upstream of exon 2.

Proteins

Atlas Image
Schematic representation of human tenascin-W is shown.

Description

Tenascin-W is built up of different structural motifs arranged in a linear order, namely amino-terminal heptad repeats, 3.5 EGF-like repeats, 9 FN III domains, and a carboxyl-terminal fibrinogen globe.
The primary sequence encodes a protein of 1294 amino acids. Amino acids 1-16 represent the secretion signal, amino acids 150-254 constitute the EGF-like repeats, and amino acids 255-1054 account for the FNIII domains. FN III domain number 3 was subject to duplication as indicated by the dark boxes in the schematic representation. Tenascin-W is known to form hexameric structures called hexabrachions.
SDS-Page analysis revealed a molecular weight of 160kDa per subunit under reducing conditions.
So far, there is no evidence for alternative splicing.

Expression

Initially, tenascin-W was identified in zebrafish where it was expressed in migrating cells of sclerotomal and neural crest origin. More recently, tenascin-W was characterized in mouse and chicken during embryogenesis as well as in the adult organism. These studies revealed that tenascin-W, similar to tenascin-C, shows tight regulation during development and in the adult. Immunohistochemistry showed prominent expression in the developing and adult metanephric kidney, developing and adult periosteum around ribs, and transient expression in smooth muscles of the developing gut, often but not always overlapping with tenascin-C expression. Furthermore, tenascin-W is highly expressed in the tumor stroma in different solid tumors.
Tenascin-W is most likely produced and secreted by mesenchymal cells such as fibroblasts and osteoblasts.
Known stimuli that induce tenascin-W expression include so far tumor necrosis factor alpha (TNFα) and bone morphogenetic protein 2 (BMP2).

Localisation

Extracellular matrix.

Function

Adhesion: Tenascin-W is an adhesive substratum for some cells (osteoblasts, fibroblasts), while others cannot attach and spread on tenascin-W.
Migration: Tenascin-W stimulates the migratory behavior of cells.

Homology

Tenascin-W 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.
Human tenascin-W shows high sequence conservation with mouse tenascin-W.

Implicated in

Entity name
Breast cancer
Oncogenesis
Tenascin-W is highly expressed in a large fraction of breast cancer patients whereas it is not detectable in normal human mammary tissue. Expression in tumors correlated with tumor grade. There is statistically significant higher mean expression of tenascin-W in low-grade tumors (Grade1/Grade2) compared to high-grade tumors (Grade3).
Tenascin-W is produced in the stromal compartment, most likely by cancer-associated fibroblasts, which are part of a tumor permissive microenvironment that facilitates tumor cell migration. In vitro, presence of tenascin-W stimulated breast cancer cell migration.
Benign tumors as well as carcinomas do express tenascin-W.
Furthermore, tenascin-W is elevated in sera of breast cancer patients compared to that of healthy volunteers.
Tenascin-W is postulated to be a marker for conversion of the normal physiological stroma to an activated stroma in breast cancer.
Entity name
Colorectal cancer
Oncogenesis
Tenascin-W is highly expressed in colorectal cancer patients whereas it is not detectable in the normal colon mucosa. Furthermore, mean tenascin-W level in sera of colorectal cancer patients is statistically increased compared to that in sera of healthy volunteers. Follow-up studies of colorectal cancer patients revealed that 4 out of 5 patients who developed tumor recurrence after treatment showed high tenascin-W levels in their sera. Thus, tenascin-W might have prognostic value as a serum tumor marker.

Bibliography

Pubmed IDLast YearTitleAuthors
165347822006Avian tenascin-W: expression in smooth muscle and bone, and effects on calvarial cell spreading and adhesion in vitro.Meloty-Kapella CV et al
155924962005Tenascin-W is found in malignant mammary tumors, promotes alpha8 integrin-dependent motility and requires p38MAPK activity for BMP-2 and TNF-alpha induced expression in vitro.Scherberich A et al
168934612006Phylogenetic analysis of the tenascin gene family: evidence of origin early in the chordate lineage.Tucker RP et al
95521621998Zebrafish tenascin-W, a new member of the tenascin family.Weber P et al

Other Information

Locus ID:

NCBI: 63923
MIM: 617472
HGNC: 22942
Ensembl: ENSG00000120332

Variants:

dbSNP: 63923
ClinVar: 63923
TCGA: ENSG00000120332
COSMIC: TNN

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000120332ENST00000239462Q9UQP3
ENSG00000120332ENST00000621086A0A087WXC4
ENSG00000120332ENST00000622870A0A087WXT0

Expression (GTEx)

0
1
2
3
4
5
6
7

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
ECM proteoglycansREACTOMER-HSA-3000178

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
155924962005Tenascin-W is found in malignant mammary tumors, promotes alpha8 integrin-dependent motility and requires p38MAPK activity for BMP-2 and TNF-alpha induced expression in vitro.33
179090222007Tenascin-W is a novel marker for activated tumor stroma in low-grade human breast cancer and influences cell behavior.22
266278732016Targeted next-generation sequencing assay for detection of mutations in primary myopathies.22
183063552008Tenascin-W, a new marker of cancer stroma, is elevated in sera of colon and breast cancer patients.14
258687082015Transcriptional regulation of tenascin-W by TGF-beta signaling in the bone metastatic niche of breast cancer cells.12
286299002017Multiple analyses indicate the specific association of NR1I3, C6 and TNN with low hip BMD risk.1

Citation

Martin Degen ; Ruth Chiquet-Ehrismann

TNN (tenascin N)

Atlas Genet Cytogenet Oncol Haematol. 2008-02-01

Online version: http://atlasgeneticsoncology.org/gene/44209/tnn