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TNN (tenascin N)

Identity

Other namesTN-W
TN-N
HGNC (Hugo) TNN
Location 1q25.1
Location_base_pair Starts at 173303617 and ends at 173383825 bp from pter ( according to hg18-Mar_2006)  [Mapping]
Local_order tail to tail configuration next to the tenascin-R gene(TNR)

DNA/RNA

 
  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.

Protein

 
  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 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 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.
  

External links

Nomenclature
HGNC (Hugo)TNN   22942
Entrez_Gene (NCBI)TNN  63923  tenascin N
Cards
AtlasTNNID44209ch1q25
GeneCards (Weizmann)TNN
Ensembl (Hinxton)ENSG00000120332 [Gene_View]  TNN [Vega]
AceView (NCBI)TNN
Genatlas (Paris)TNN
euGene (Indiana)63923
SOURCE (Stanford)NM_022093
Gene Expression (Array Express) ENSG00000120332
Genomic and cartography
GoldenPath (UCSC)TNN  -  1q25.1   chr1:173303617-173383825 +  1q23-q24   [Description]    (hg18-Mar_2006)
EnsemblTNN - 1q23-q24 [CytoView]
Mapping of homologs : NCBITNN [Mapview]
OMIM
Gene and transcription
Gene : Genbank (Entrez)AK127044 AK127654 AL049689 BC136619 BC144305
Reference sequence (RefSeq transcript) :SRSNM_022093
Reference transcript : EntrezNM_022093
RefSeq genomic : SRSAC_000044 AC_000133 NC_000001 NT_004487 NW_001838533 NW_926128
RefSeq genomic : EntrezAC_000044 AC_000133 NC_000001 NT_004487 NW_001838533 NW_926128
Consensus coding sequences : CCDS NCBITNN
Cluster EST : UnigeneHs.156369 [ SRS ] Hs.156369 [ NCBI ]
Alternative Splicing : Fast-db (Paris)17591
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtQ9UQP3 (SRS) Q9UQP3 (Expasy) Q9UQP3 (Uniprot)
With graphics : InterProQ9UQP3
Splice isoforms : VarSplice FASTAQ9UQP3(VarSplice FASTA)
Domaine pattern : Prosite (SRS)EGF_1 (PS00022)    EGF_2 (PS01186)    EGF_3 (PS50026)    FIBRINOGEN_C_1 (PS00514)    FIBRINOGEN_C_2 (PS51406)    FN3 (PS50853)   
Domain pattern : Prosite (Expaxy)EGF_1 (PS00022)    EGF_2 (PS01186)    EGF_3 (PS50026)    FIBRINOGEN_C_1 (PS00514)    FIBRINOGEN_C_2 (PS51406)    FN3 (PS50853)   
Domains : Interpro (SRS)EGF-like_reg_CS    EGF_extracell    Fibrinogen_a/b/g_C    Fibrinogen_CS    Fibronectin_typ-III-like_fold    FN_III   
Domains : Interpro (EBI)EGF-like_reg_CS    EGF_extracell    Fibrinogen_a/b/g_C    Fibrinogen_CS    Fibronectin_typ-III-like_fold    FN_III   
Related proteins : CluSTrQ9UQP3
Domain families : Pfam SRSEGF_2 (PF07974)    Fibrinogen_C (PF00147)    fn3 (PF00041)   
Domain families : Pfam SangerEGF_2 (PF07974)    Fibrinogen_C (PF00147)    fn3 (PF00041)   
Domain families : Pfam NCBIpfam07974    pfam00147    pfam00041   
Domain families : Smart EMBLFBG (SM00186)  FN3 (SM00060)  
Blocks (Seattle)Q9UQP3
Crystal structure of protein : PDB SRS
Crystal structure of protein : PDBSum
Crystal structure of protein : IMB
Crystal structure of protein : PDB RSDB
Protein Interaction databases
DIP (DOE-UCLA)Q9UQP3
IntAct (EBI)Q9UQP3
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBITNN
SNP : GeneSNP UtahTNN
SNP : HGBaseTNN
Genetic variants : HAPMAPTNN
Mutations and Diseases : HGMDTNN
Hereditary diseases : OMIM
Hereditary diseases : GENETests
Diseases : Genetic AssociationTNN
General knowledge
Homologs : HomoloGeneTNN
Homology/Alignments : Family Browser UCSCTNN
Phylogenetic Trees/Animal Genes : TreeFamTNN
Chemical/Protein Interactions : CTD63923
Keywords Ontology : AmiGOmolecular_function  integrin binding  cellular_component  proteinaceous extracellular matrix  extracellular space  cell-matrix adhesion  signal transduction  axonogenesis  cell surface  cell growth  cell migration  identical protein binding  
Keywords Ontology : EGO-EBImolecular_function  integrin binding  cellular_component  proteinaceous extracellular matrix  extracellular space  cell-matrix adhesion  signal transduction  axonogenesis  cell surface  cell growth  cell migration  identical protein binding  
Pathways : BIOCARTA
Pathways : KEGGCell CommunicationFocal adhesionECM-receptor interaction
Other databases
Probes
Probes : ImagenesTNN Related clones (RZPD - Berlin)
Literature
PubMed8 Pubmed reference(s) in Entrez
PubGeneTNN

Bibliography

Zebrafish tenascin-W, a new member of the tenascin family.
Weber P, Montag D, Schachner M.
J Neurobiol. 1998 Apr;35(1):1-16.
PMID 9552162
 
Murine tenascin-W: a novel mammalian tenascin expressed in kidney and at sites of bone and smooth muscle development.
Scherberich A, Tucker RP, Samandari E, Brown-Luedi M, Martin D, Chiquet-Ehrismann R.
J Cell Sci. 2004 Feb 1;117(Pt 4):571-81. Epub 2004 Jan 6.
PMID 14709716
 
Tenascin-W is found in malignant mammry tumors, promotes alpha8 integrin-dependent motility and requires p38MAPK activity for BMP-2 and TNF alpha induced expression in vitro.
Scherberich A, Tucker RP, Degen M, Brown-Luedi M, Andres AC, Chiquet-Ehrismann R.
Oncogene. 2005 Feb 24;24(9):1525-32.
PMID 15592496
 
Avian tenascin-W: expression in smooth muscle and bone, and effects on calvarial cell spreading and adhesion in vitro.
Meloty-Kapella C, Degen M, Chiquet-Ehrismann R, Tucker RP.
Dev Dyn. 2006 Jun;235(6):1532-42.
PMID 16534782
 
Phylogenetic analysis of the tenascin gene family: evidence of origin early in the chordate lineage.
Tucker RP, Drabikowski K, Hess JF, Ferralli J, Chiquet-Ehrismann R, Adams JC.
BMC Evol Biol. 2006 Aug 7;6:60.
PMID 16893461
 
Tenascin-W is a novel marker for activated tumor stroma in low-grade human breast cancer and influences cell behavior.
Degen M, Brellier F, Kain R, Ruiz C, Terracciano L, Orend G, Chiquet-Ehrismann R.
Canc Res 2007; 67: 9169-9179.
PMID 17909022
 
Tenascin-W, a new marker of cancer stroma, is elevated in sera of colon and breast cancer patients.
Degen M, Brellier F, Schenk S, Driscoll R, Zaman K, Stupp R, Tornillo L, Terracciano L, Chiquet-Ehrismann R, Rüegg C, Seelentag W.
Int J Cancer in press.
 
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 . TNN (tenascin N). Atlas Genet Cytogenet Oncol Haematol. February 2008 .
URL : http://AtlasGeneticsOncology.org/Genes/TNNID44209ch1q25.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Sat Feb 27 10:49:51 CET 2010

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