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TNS4 (tensin 4)

Written2012-04Saleh Al-Ghamdi, Mohammad Ilyas
Division of Pathology, Nottingham University, Nottingham, UK (SAG, MI); King Abdullah International Medical Research Center, National Guard Health Affairs, Riyadh 11426, Saudi Arabia (SAG); Nottingham Digestive Diseases Centre, NIHR Biomedical Research Unit, Queen's Medical Centre, Nottingham University Hospitals NHS Trust, Nottingham, UK (MI)

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)CTEN
Other alias
HGNC (Hugo) TNS4
LocusID (NCBI) 84951
Atlas_Id 40190
Location 17q21.2  [Link to chromosome band 17q21]
Location_base_pair Starts at 40475828 and ends at 40501602 bp from pter ( according to hg19-Feb_2009)  [Mapping TNS4.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
BORCS7 (10q24.32) / TNS4 (17q21.2)MASP1 (3q27.3) / TNS4 (17q21.2)TNS4 (17q21.2) / GPRC5B (16p12.3)
TNS4 (17q21.2) / TNS4 (17q21.2)
Note The TNS4 gene was identified by Lo and Lo. They found that it is composed of 12 exons encoding an mRNA of 4015 bp with an open reading frame encoding 715 amino acid residues. The amino acids 418-715 are very similar to the COOH termini of tensin 1, tensin 2 and tensin 3. There are six potential tyrosine phosphorylation sites found in TNS4 although the gene product is a shorter polypeptide and lacks the NH2-terminal homologous regions found in tensins. This gene was found to be distant member of the tensin family and given name cten for the COOH-terminal tensin-like molecule.

DNA/RNA

Note It was found that the human cten gene is located on chromosome 17q12-21 and has 12 exons. The SH2 domains bind ligands containing pTyr residues within a specific sequence and high affinity binding is provided by the pTyr residue itself and by subsequent residues toward the COOH-terminal.
 
  Figure 1. Analysis of cten amino acid sequence. A. The cDNA-derived amino acid sequence of human cten. The potential tyrosine phosphorylation sites are in bold. B. Organization of human cten gene. Exon/intron boundaries were determined by comparison of sequences of genomic DNA and cDNA. In the splice site, exon sequences are indicated by uppercase letters, and intron sequences are indicated by lowercase letters. Codon phase refers to the codon split at the splice acceptor. Introns that do not split codon triplets are indicated by phase 0, interruption after the first nucleotide is indicated by codon phase I, and interruption after the second nucleotide is indicated by codon phase II. N indicates noncoding region. Numbers in the brackets indicate the sizes of the corresponding exons in human tensin 1 and tensin 2, respectively.

Protein

Note TNS4, as the others tensins, contains a phosphotyrosine-binding domain (PTB), which plays the role of interacting with the cytoplasmic tail of the β-integrin. Also they all contain, at the C-terminal, Src homology domain 2 (SH2 domain). While tensin 1, tensin 2 and tensin 3 interact with actin at multiple sites in the N-terminal, tensin 4 (Cten) lacks the n-terminal region actin binding domain (ABD). TNS4 has only one focal adhesion binding (FAB) domains in C- terminal while others have it in both N- and C-terminals.
 
  Figure 2. Schematic structure of tensins. The C-terminus of tensin contains SH2 and PTB domains, allowing TNS4 to interact with tyrosine-phosphorylated proteins and β integrin respectively. The FAB domain is present in the C-terminal region, and it involved in mediating binding of tensin 4 to other focal adhesion molecules.
Expression The expression of Cten messenger RNA (mRNA) was evaluated in normal tissues by K. Sakashita et al. using the human total RNA master panel and found that Cten is expressed at high levels in prostate, oesophagus, breast and salivary glands. Moderate Cten expression was found in the thyroid and trachea. In contrast, very low expression was reported in colon, lung, small intestine, spleen, kidney, stomach and testis.
Localisation It is localized to focal adhesions.
Function The TNS4 is having a role in the cell motility by enhancing the migration as well as the invasion too. Also TNS4 is found to play a central role in HGF-induced tubulogenesis. The role of TNS4 on cell proliferation is found to be minimal and not up to the level of the effect of migration. By enhancing the motility and having the effect on the tubulogenesis, TNS4 is believed to have a role in cancer cell metastasis.

Mutations

Note No mutation has been reported.

Implicated in

Note
  
Entity Various cancers
Note The role of cten in cancer is not well defined. In prostate cancer it is down-regulated, where in normal cells it is localized to focal adhesions recruiting the tumour suppressor, deleted in liver cancer (DLC-1), thus suppressing tumorigenesis. Cten in prostate epithelial cells has also been found to regulate staurosporine-induced apoptosis where cten is cleaved by caspase 3 and results in reduction in cell growth rate. Therefore, loss of cten expression may lead to uncontrolled cell growth and result in cell transformation. Accordingly, in prostate cancer, cten may function as a tumour suppressor protein.
On the other hand, cten has been found to be up-regulated in a number of cancers. It is up-regulated in lung cancer and correlates with tumour progression. In breast cancer, the epidermal growth factor receptor (EGFR), which is involved in various cellular processes including proliferation and motility, up-regulates cten and down-regulates tensin 3. Tensin 3 is localized in cell matrix adhesions but it disappears upon EGF stimulation. These findings showed that EGF-induced up-regulation of cten and down-regulation of tensin 3 correlates with cten fibre remodelling. Cten disassembles actin stress fibres through its PTB domain which competes with tensin 3 for the cytoplasmic tail of integrins displacing it from focal adhesion sites. Indeed, cten in breast cancer is a potential marker of a poorly differentiated relatively aggressive sub-population of invasive breast tumours.
In colorectal cancer (CRC) and pancreatic cancer, cten has also been found to be up-regulated and is localized to both cytoplasm and nucleus. It is regulated by Kras signalling (and probably EGFR upstream of Kras) and possibly by Stat3 signalling.
  

Bibliography

Cten is targeted by Kras signalling to regulate cell motility in the colon and pancreas.
Al-Ghamdi S, Albasri A, Cachat J, Ibrahem S, Muhammad BA, Jackson D, Nateri AS, Kindle KB, Ilyas M.
PLoS One. 2011;6(6):e20919. Epub 2011 Jun 16.
PMID 21698197
 
Cten signals through integrin-linked kinase (ILK) and may promote metastasis in colorectal cancer.
Albasri A, Al-Ghamdi S, Fadhil W, Aleskandarany M, Liao YC, Jackson D, Lobo DN, Lo SH, Kumari R, Durrant L, Watson S, Kindle KB, Ilyas M.
Oncogene. 2011 Jun 30;30(26):2997-3002. doi: 10.1038/onc.2011.26. Epub 2011 Feb 21.
PMID 21339732
 
C-terminal Tensin-like (CTEN) is an oncogene which alters cell motility possibly through repression of E-cadherin in colorectal cancer.
Albasri A, Seth R, Jackson D, Benhasouna A, Crook S, Nateri AS, Chapman R, Ilyas M.
J Pathol. 2009 May;218(1):57-65.
PMID 19214987
 
Constitutively active Stat3 enhances neu-mediated migration and metastasis in mammary tumors via upregulation of Cten.
Barbieri I, Pensa S, Pannellini T, Quaglino E, Maritano D, Demaria M, Voster A, Turkson J, Cavallo F, Watson CJ, Provero P, Musiani P, Poli V.
Cancer Res. 2010 Mar 15;70(6):2558-67. Epub 2010 Mar 9.
PMID 20215508
 
Deleted in liver cancer 1 (DLC1) utilizes a novel binding site for Tensin2 PTB domain interaction and is required for tumor-suppressive function.
Chan LK, Ko FC, Ng IO, Yam JW.
PLoS One. 2009;4(5):e5572. Epub 2009 May 15.
PMID 19440389
 
A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration.
Katz M, Amit I, Citri A, Shay T, Carvalho S, Lavi S, Milanezi F, Lyass L, Amariglio N, Jacob-Hirsch J, Ben-Chetrit N, Tarcic G, Lindzen M, Avraham R, Liao YC, Trusk P, Lyass A, Rechavi G, Spector NL, Lo SH, Schmitt F, Bacus SS, Yarden Y.
Nat Cell Biol. 2007 Aug;9(8):961-9. Epub 2007 Jul 22.
PMID 17643115
 
Transcriptional profiling identifies TNS4 function in epithelial tubulogenesis.
Kwon SH, Nedvetsky PI, Mostov KE.
Curr Biol. 2011 Jan 25;21(2):161-6. Epub 2011 Jan 13.
PMID 21236678
 
CTEN/tensin 4 expression induces sensitivity to paclitaxel in prostate cancer.
Li Y, Mizokami A, Izumi K, Narimoto K, Shima T, Zhang J, Dai J, Keller ET, Namiki M.
Prostate. 2010 Jan 1;70(1):48-60.
PMID 19725034
 
Up-regulation of C-terminal tensin-like molecule promotes the tumorigenicity of colon cancer through beta-catenin.
Liao YC, Chen NT, Shih YP, Dong Y, Lo SH.
Cancer Res. 2009 Jun 1;69(11):4563-6.
PMID 19487278
 
The phosphotyrosine-independent interaction of DLC-1 and the SH2 domain of cten regulates focal adhesion localization and growth suppression activity of DLC-1.
Liao YC, Si L, deVere White RW, Lo SH.
J Cell Biol. 2007 Jan 1;176(1):43-9. Epub 2006 Dec 26.
PMID 17190795
 
Cten, a COOH-terminal tensin-like protein with prostate restricted expression, is down-regulated in prostate cancer.
Lo SH, Lo TB.
Cancer Res. 2002 Aug 1;62(15):4217-21.
PMID 12154022
 
Cleavage of cten by caspase-3 during apoptosis.
Lo SS, Lo SH, Lo SH.
Oncogene. 2005 Jun 16;24(26):4311-4.
PMID 15806167
 
Prognostic relevance of Tensin4 expression in human gastric cancer.
Sakashita K, Mimori K, Tanaka F, Kamohara Y, Inoue H, Sawada T, Hirakawa K, Mori M.
Ann Surg Oncol. 2008 Sep;15(9):2606-13. Epub 2008 Jul 9.
PMID 18612693
 
Cten mRNA expression was correlated with tumor progression in lung cancers.
Sasaki H, Moriyama S, Mizuno K, Yukiue H, Konishi A, Yano M, Kaji M, Fukai I, Kiriyama M, Yamakawa Y, Fujii Y.
Lung Cancer. 2003 May;40(2):151-5.
PMID 12711115
 
Cten mRNA expression is correlated with tumor progression in thymoma.
Sasaki H, Yukiue H, Kobayashi Y, Fukai I, Fujii Y.
Tumour Biol. 2003 Sep-Oct;24(5):271-4.
PMID 15001839
 

Citation

This paper should be referenced as such :
Al-Ghamdi, S ; Ilyas, M
TNS4 (tensin 4)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(10):703-705.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/TNS4ID40190ch17q21.html


External links

Nomenclature
HGNC (Hugo)TNS4   24352
Cards
AtlasTNS4ID40190ch17q21
Entrez_Gene (NCBI)TNS4  84951  tensin 4
AliasesCTEN; PP14434
GeneCards (Weizmann)TNS4
Ensembl hg19 (Hinxton)ENSG00000131746 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000131746 [Gene_View]  chr17:40475828-40501602 [Contig_View]  TNS4 [Vega]
ICGC DataPortalENSG00000131746
TCGA cBioPortalTNS4
AceView (NCBI)TNS4
Genatlas (Paris)TNS4
WikiGenes84951
SOURCE (Princeton)TNS4
Genetics Home Reference (NIH)TNS4
Genomic and cartography
GoldenPath hg38 (UCSC)TNS4  -     chr17:40475828-40501602 -  17q21.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)TNS4  -     17q21.2   [Description]    (hg19-Feb_2009)
EnsemblTNS4 - 17q21.2 [CytoView hg19]  TNS4 - 17q21.2 [CytoView hg38]
Mapping of homologs : NCBITNS4 [Mapview hg19]  TNS4 [Mapview hg38]
OMIM608385   
Gene and transcription
Genbank (Entrez)AF370421 AF417488 AK027856 AW378527 AW937802
RefSeq transcript (Entrez)NM_032865
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)TNS4
Cluster EST : UnigeneHs.438292 [ NCBI ]
CGAP (NCI)Hs.438292
Alternative Splicing GalleryENSG00000131746
Gene ExpressionTNS4 [ NCBI-GEO ]   TNS4 [ EBI - ARRAY_EXPRESS ]   TNS4 [ SEEK ]   TNS4 [ MEM ]
Gene Expression Viewer (FireBrowse)TNS4 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)84951
GTEX Portal (Tissue expression)TNS4
Human Protein AtlasENSG00000131746-TNS4 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8IZW8   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8IZW8  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8IZW8
Splice isoforms : SwissVarQ8IZW8
PhosPhoSitePlusQ8IZW8
Domaine pattern : Prosite (Expaxy)SH2 (PS50001)   
Domains : Interpro (EBI)PH_dom-like    PTB    PTB/PI_dom    SH2    Tensin_PTB   
Domain families : Pfam (Sanger)PTB (PF08416)    SH2 (PF00017)   
Domain families : Pfam (NCBI)pfam08416    pfam00017   
Domain families : Smart (EMBL)PTB (SM00462)  SH2 (SM00252)  
Conserved Domain (NCBI)TNS4
DMDM Disease mutations84951
Blocks (Seattle)TNS4
SuperfamilyQ8IZW8
Human Protein Atlas [tissue]ENSG00000131746-TNS4 [tissue]
Peptide AtlasQ8IZW8
HPRD12223
IPIIPI00170752   IPI00449075   
Protein Interaction databases
DIP (DOE-UCLA)Q8IZW8
IntAct (EBI)Q8IZW8
FunCoupENSG00000131746
BioGRIDTNS4
STRING (EMBL)TNS4
ZODIACTNS4
Ontologies - Pathways
QuickGOQ8IZW8
Ontology : AmiGOactin binding  protein binding  cytosol  cytoskeleton  focal adhesion  apoptotic process  protein localization  
Ontology : EGO-EBIactin binding  protein binding  cytosol  cytoskeleton  focal adhesion  apoptotic process  protein localization  
REACTOMEQ8IZW8 [protein]
REACTOME PathwaysR-HSA-8875513 [pathway]   
NDEx NetworkTNS4
Atlas of Cancer Signalling NetworkTNS4
Wikipedia pathwaysTNS4
Orthology - Evolution
OrthoDB84951
GeneTree (enSembl)ENSG00000131746
Phylogenetic Trees/Animal Genes : TreeFamTNS4
HOVERGENQ8IZW8
HOGENOMQ8IZW8
Homologs : HomoloGeneTNS4
Homology/Alignments : Family Browser (UCSC)TNS4
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerTNS4 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)TNS4
dbVarTNS4
ClinVarTNS4
1000_GenomesTNS4 
Exome Variant ServerTNS4
ExAC (Exome Aggregation Consortium)ENSG00000131746
GNOMAD BrowserENSG00000131746
Genetic variants : HAPMAP84951
Genomic Variants (DGV)TNS4 [DGVbeta]
DECIPHERTNS4 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisTNS4 
Mutations
ICGC Data PortalTNS4 
TCGA Data PortalTNS4 
Broad Tumor PortalTNS4
OASIS PortalTNS4 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICTNS4  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDTNS4
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
BioMutasearch TNS4
DgiDB (Drug Gene Interaction Database)TNS4
DoCM (Curated mutations)TNS4 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)TNS4 (select a term)
intoGenTNS4
NCG5 (London)TNS4
Cancer3DTNS4(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM608385   
Orphanet
MedgenTNS4
Genetic Testing Registry TNS4
NextProtQ8IZW8 [Medical]
TSGene84951
GENETestsTNS4
Target ValidationTNS4
Huge Navigator TNS4 [HugePedia]
snp3D : Map Gene to Disease84951
BioCentury BCIQTNS4
ClinGenTNS4
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD84951
Chemical/Pharm GKB GenePA142670717
Clinical trialTNS4
Miscellaneous
canSAR (ICR)TNS4 (select the gene name)
Probes
Litterature
PubMed35 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineTNS4
EVEXTNS4
GoPubMedTNS4
iHOPTNS4
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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