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.
Proteins
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
Entity name
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.
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 21698197 | 2011 | Cten is targeted by Kras signalling to regulate cell motility in the colon and pancreas. | Al-Ghamdi S et al |
| 21339732 | 2011 | Cten signals through integrin-linked kinase (ILK) and may promote metastasis in colorectal cancer. | Albasri A et al |
| 19214987 | 2009 | C-terminal Tensin-like (CTEN) is an oncogene which alters cell motility possibly through repression of E-cadherin in colorectal cancer. | Albasri A et al |
| 20215508 | 2010 | Constitutively active Stat3 enhances neu-mediated migration and metastasis in mammary tumors via upregulation of Cten. | Barbieri I et al |
| 19440389 | 2009 | 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 et al |
| 17643115 | 2007 | A reciprocal tensin-3-cten switch mediates EGF-driven mammary cell migration. | Katz M et al |
| 21236678 | 2011 | Transcriptional profiling identifies TNS4 function in epithelial tubulogenesis. | Kwon SH et al |
| 19725034 | 2010 | CTEN/tensin 4 expression induces sensitivity to paclitaxel in prostate cancer. | Li Y et al |
| 19487278 | 2009 | Up-regulation of C-terminal tensin-like molecule promotes the tumorigenicity of colon cancer through beta-catenin. | Liao YC et al |
| 17190795 | 2007 | 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 et al |
| 12154022 | 2002 | Cten, a COOH-terminal tensin-like protein with prostate restricted expression, is down-regulated in prostate cancer. | Lo SH et al |
| 15806167 | 2005 | Cleavage of cten by caspase-3 during apoptosis. | Lo SS et al |
| 18612693 | 2008 | Prognostic relevance of Tensin4 expression in human gastric cancer. | Sakashita K et al |
| 12711115 | 2003 | Cten mRNA expression was correlated with tumor progression in lung cancers. | Sasaki H et al |
| 15001839 | 2003 | Cten mRNA expression is correlated with tumor progression in thymoma. | Sasaki H et al |
Other Information
Locus ID:
NCBI: 84951
MIM: 608385
HGNC: 24352
Ensembl: ENSG00000131746
Variants:
dbSNP: 84951
ClinVar: 84951
TCGA: ENSG00000131746
COSMIC: TNS4
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000131746 | ENST00000254051 | Q8IZW8 |
| ENSG00000131746 | ENST00000582747 | J3QLA4 |
Expression (GTEx)
Pathways
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 36399312 | 2023 | Nuclear-localized CTEN is a novel transcriptional regulator and promotes cancer cell migration through its downstream target CDC27. | 1 |
| 36896596 | 2023 | Epigenetic Activation of Tensin 4 Promotes Gastric Cancer Progression. | 2 |
| 36399312 | 2023 | Nuclear-localized CTEN is a novel transcriptional regulator and promotes cancer cell migration through its downstream target CDC27. | 1 |
| 36896596 | 2023 | Epigenetic Activation of Tensin 4 Promotes Gastric Cancer Progression. | 2 |
| 36281194 | 2022 | Mining TCGA and GEO databases for the prediction of poor prognosis in lung adenocarcinoma based on up-regulated expression of TNS4. | 0 |
| 36281194 | 2022 | Mining TCGA and GEO databases for the prediction of poor prognosis in lung adenocarcinoma based on up-regulated expression of TNS4. | 0 |
| 33310188 | 2021 | Histone acetyltransferase p300 mediates the upregulation of CTEN induced by the activation of EGFR signaling in cancer cells. | 4 |
| 34817293 | 2021 | CTEN Inhibits Tumor Angiogenesis and Growth by Targeting VEGFA Through Down-Regulation of β-Catenin in Breast Cancer. | 5 |
| 33310188 | 2021 | Histone acetyltransferase p300 mediates the upregulation of CTEN induced by the activation of EGFR signaling in cancer cells. | 4 |
| 34817293 | 2021 | CTEN Inhibits Tumor Angiogenesis and Growth by Targeting VEGFA Through Down-Regulation of β-Catenin in Breast Cancer. | 5 |
| 32390347 | 2020 | Investigating TNS4 in the Colorectal Tumor Microenvironment Using 3D Spheroid Models of Invasion. | 6 |
| 32534709 | 2020 | Tensin4 promotes invasion and migration of gastric cancer cells via regulating AKT/GSK-3β/snail signaling pathway. | 10 |
| 32390347 | 2020 | Investigating TNS4 in the Colorectal Tumor Microenvironment Using 3D Spheroid Models of Invasion. | 6 |
| 32534709 | 2020 | Tensin4 promotes invasion and migration of gastric cancer cells via regulating AKT/GSK-3β/snail signaling pathway. | 10 |
| 30321615 | 2019 | Identification of subcellular targeting sequences of Cten reveals its role in cell proliferation. | 6 |
Citation
Saleh Al-Ghamdi ; Mohammad Ilyas
TNS4 (tensin 4)
Atlas Genet Cytogenet Oncol Haematol. 2012-04-01
Online version: http://atlasgeneticsoncology.org/gene/40190/tns4-(tensin-4)
