Download Gene Section TNS4 (tensin 4) Atlas of Genetics and Cytogenetics

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Gene Section
Short Communication
TNS4 (tensin 4)
Saleh Al-Ghamdi, Mohammad Ilyas
King Abdullah International Medical Research Center, National Guard Health Affairs, Riyadh 11426, Saudi
Arabia; Division of Pathology, Nottingham University, Nottingham, UK (SAG), Nottingham Digestive
Diseases Centre, NIHR Biomedical Research Unit, Queen's Medical Centre, Nottingham University
Hospitals NHS Trust, Nottingham, UK; Division of Pathology, Nottingham University, Nottingham, UK
(MI)
Published in Atlas Database: April 2012
Online updated version : http://AtlasGeneticsOncology.org/Genes/TNS4ID40190ch17q21.html
DOI: 10.4267/2042/48143
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2012 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Identity
DNA/RNA
Other names: CTEN
HGNC (Hugo): TNS4
Location: 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 NH2terminal 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.
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.
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(10)
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 βintegrin.
Also they all contain, at the C-terminal, Src homology
domain 2 (SH2 domain).
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TNS4 (tensin 4)
Al-Ghamdi S, Ilyas M
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.
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.
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 Nand C-terminals.
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
Expression
It is localized to focal adhesions.
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,
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(10)
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-
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TNS4 (tensin 4)
Al-Ghamdi S, Ilyas M
Sasaki H, Yukiue H, Kobayashi Y, Fukai I, Fujii Y. Cten mRNA
expression is correlated with tumor progression in thymoma.
Tumour Biol. 2003 Sep-Oct;24(5):271-4
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.
Lo SS, Lo SH, Lo SH. Cleavage of cten by caspase-3 during
apoptosis. Oncogene. 2005 Jun 16;24(26):4311-4
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. A
reciprocal tensin-3-cten switch mediates EGF-driven mammary
cell migration. Nat Cell Biol. 2007 Aug;9(8):961-9
Mutations
Note
No mutation has been reported.
Liao YC, Si L, deVere White RW, Lo SH. The phosphotyrosineindependent interaction of DLC-1 and the SH2 domain of cten
regulates focal adhesion localization and growth suppression
activity of DLC-1. J Cell Biol. 2007 Jan 1;176(1):43-9
Implicated in
Various cancers
Sakashita K, Mimori K, Tanaka F, Kamohara Y, Inoue H,
Sawada T, Hirakawa K, Mori M. Prognostic relevance of
Tensin4 expression in human gastric cancer. Ann Surg Oncol.
2008 Sep;15(9):2606-13
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 upregulated 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 subpopulation 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.
Albasri A, Seth R, Jackson D, Benhasouna A, Crook S, Nateri
AS, Chapman R, Ilyas M. C-terminal Tensin-like (CTEN) is an
oncogene which alters cell motility possibly through repression
of E-cadherin in colorectal cancer. J Pathol. 2009
May;218(1):57-65
Chan LK, Ko FC, Ng IO, Yam JW. Deleted in liver cancer 1
(DLC1) utilizes a novel binding site for Tensin2 PTB domain
interaction and is required for tumor-suppressive function.
PLoS One. 2009;4(5):e5572
Liao YC, Chen NT, Shih YP, Dong Y, Lo SH. Up-regulation of
C-terminal tensin-like molecule promotes the tumorigenicity of
colon cancer through beta-catenin. Cancer Res. 2009 Jun
1;69(11):4563-6
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. Constitutively active Stat3
enhances neu-mediated migration and metastasis in mammary
tumors via upregulation of Cten. Cancer Res. 2010 Mar
15;70(6):2558-67
Li Y, Mizokami A, Izumi K, Narimoto K, Shima T, Zhang J, Dai
J, Keller ET, Namiki M. CTEN/tensin 4 expression induces
sensitivity to paclitaxel in prostate cancer. Prostate. 2010 Jan
1;70(1):48-60
Albasri A, Aleskandarany M, Benhasouna A, Powe DG, Ellis
IO, Ilyas M, Green AR. CTEN (C-terminal tensin-like), a novel
oncogene overexpressed in invasive breast carcinoma of poor
prognosis. Breast Cancer Res Treat. 2011 Feb;126(1):47-54
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. Cten signals through integrin-linked kinase
(ILK) and may promote metastasis in colorectal cancer.
Oncogene. 2011 Jun 30;30(26):2997-3002
Al-Ghamdi S, Albasri A, Cachat J, Ibrahem S, Muhammad BA,
Jackson D, Nateri AS, Kindle KB, Ilyas M. Cten is targeted by
Kras signalling to regulate cell motility in the colon and
pancreas. PLoS One. 2011;6(6):e20919
Kwon SH, Nedvetsky PI, Mostov KE. Transcriptional profiling
identifies TNS4 function in epithelial tubulogenesis. Curr Biol.
2011 Jan 25;21(2):161-6
References
Lo SH, Lo TB. Cten, a COOH-terminal tensin-like protein with
prostate restricted expression, is down-regulated in prostate
cancer. Cancer Res. 2002 Aug 1;62(15):4217-21
This article should be referenced as such:
Al-Ghamdi S, Ilyas M. TNS4 (tensin 4). Atlas Genet Cytogenet
Oncol Haematol. 2012; 16(10):703-705.
Sasaki H, Moriyama S, Mizuno K, Yukiue H, Konishi A, Yano
M, Kaji M, Fukai I, Kiriyama M, Yamakawa Y, Fujii Y. Cten
mRNA expression was correlated with tumor progression in
lung cancers. Lung Cancer. 2003 May;40(2):151-5
Atlas Genet Cytogenet Oncol Haematol. 2012; 16(10)
705