Download Gene Section TACSTD1 (tumor-associated calcium signal transducer 1) Atlas of Genetics and Cytogenetics

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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Gene Section
Mini Review
TACSTD1 (tumor-associated calcium signal
transducer 1)
Olivier Gires
Clinical Cooperation Group Molecular Oncology, Munich Medical Center, Ludwig-Maximilians-University,
Marchioninistr. 15, D-81377 Munich, Germany, and HelmholtzZentrum munchen, German Research Center
for Environmental Health, Marchioninistr. 25, D-81377 Munich, Germany
Published in Atlas Database: February 2008
Online updated version: http://AtlasGeneticsOncology.org/Genes/TACSTD1ID42459ch2p21.html
DOI: 10.4267/2042/38601
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence.
© 2008 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Localisation
Identity
Plasma membrane; baso-lateral in normal cells;
redistribution on entire plasma membrane in vitro and
in carcinoma cells.
Hugo: TACSTD1
Other names: EpCAM; Ep-CAM; CD326; CO17-1A;
EGP; EGP40; GA733-2; KSA; Ly74; M1S2; M4S1;
MIC18; MK-1; TROP1; hEGP-2
Location: 2p21
Function
Homophilic cell-to-cell adhesion molecule (Litvinov et
al., 1994); regulation of cadherin-mediated cell-to-cell
adhesion (Litvinov et al., 1997); oncogenic signalling
molecule, which is over-expressed in a plethora of
carcinomas (Baeuerle and Gires, 2007); induces cell
proliferation via induction of the proto-oncogene c-myc
(Munz et al., 2004); intracellular domain of TACSTD1
/EpCAM is mandatory and sufficient for induction of cmyc gene expression; inhibition results in decreased
proliferation and invasion (Osta et al., 2004); frequent
use as a prognostic marker (Went et al., 2006; Spizzo et
al., 2006) and therapeutic target (Baeuerle and Gires,
2007; RiethMüller et al., 1994; Schweizer et al., 2002;
Amann et al., 2008; Ruf et al., 2007).
DNA/RNA
Description
The gene is composed of 9 exons and encompasses.
Transcription
1.528 kb mRNA; 945 bp open reading frame from base
pairs 179 to 1123, (NM_002354).
Pseudogene
No pseudogene described so far.
Protein
Homology
Description
Retroposon GA733-1; gp50/TROP-2 (Fornaro et al.,
1995), single-copy gene localised at chrom 1p32-31
TACSTD2, Accession CAA54801, 323 amino acids,
calcium-dependent signalling protein. High homology
of TACSTD1/EpCAM to TACSTD2/TROP-2/GA7331), especially in the extracellular domain including
cystein-rich EGF-like domains, conserved region
similar to thyroglobulin type I repeat (Thyr I-like
repeat).
314 amino acids (aa); 265 aa extracellular domain, 23
aa transmembrane domain, 26 aa intracellular domain;
34-42 kDa glycoprotein; differential glycosylation in
tumours vesus normal mucosa (Pauli et al., 2003).
Expression
Restricted to epithelia; mainly in simple epithelium and
basal membrane cells; strong overexpression in
malignancies already at the stage of dysplasia (Litvinov
et al., 1996).
Atlas Genet Cytogenet Oncol Haematol. 2008;12(6)
443
TACSTD1 (tumor-associated calcium signal transducer 1)
Gires O
Increased expression of EpCAM is a marker for
decreased relapse-free survival (Stoecklein et al.,
2006).
Oncogenesis
EpCAM is strongly overexpressed.
Mutations
Note: So far, no mutations of the TACSTD1/epcam
gene were described.
Implicated in
Hepatocyte development
Colon cancer
Note: EpCAM is strongly expressed in differentiation
hepatocytes and progenitors thereof (Schmelzer et al.,
2007; Schmelzer and Reid, 2008).
Oncogenesis
EpCAM is strongly overexpressed and was used as a
molecular target for monoclonal, therapeutic antibody
17-1A (Panorex©) (RiethMüller et al., 1994).
EpCAM, in a complex with claudin-7, CD44 isoforms,
and tetraspanins, is involved in colorectal cancer
progression (Kuhn et al., 2007).
Breakpoints
Note: No breakpoints described so far.
To be noted
Breast cancer
Note: The gene name TACSTD1, for TumourAssociated Calcium Signalling Signal Transducer 1, is
highly misleading and unappropriate. EpCAM, alias
TACSTD1, is in fact a signal-transducing membrane
protein (Munz et al., 2004), however it is involved in
calcium-independent homophilic cell-to-cell adhesion
(Litvinov et al., 1994). We shall therefore propose to
use the term epcam for the gene and EpCAM for the
protein (Baeuerle and Gires, 2007).
The characterisation of the molecular function of
EpCAM in carcinoma cells pinpointed a role in
signalling and regulation of gene transcription rather
than cell-to-cell adhesion (Osta et al., 2004; Munz et
al., 2004). With respect to cell adhesion properties of
EpCAM literature is even contradictory (Fornaro et al.,
1995; Litvinov et al., 1994).
More recent work described EpCAM as a marker for
tumour-initiating cancer stem cells in a variety of
entities including colon (Dalerba et al., 2007), pancreas
(Li et al., 2007), and breast carcinomas (Al-Hajj et al.,
2003).
A symposium on functions and clinical applications of
EpCAM was initiated 2006 and will be held every two
years. For more details please visit http://www.epcamsymposium.de .
Prognosis
Increased expression of EpCAM is a marker for poor
prognosis and overall survival of patients suffering
from node-positive breast cancer (Spizzo et al., 2004).
Oncogenesis
EpCAM is strongly overexpressed.
Ovarian cancer
Prognosis
Increased expression of EpCAM is a marker for poor
prognosis and overall survival of patients suffering
from ovarian cancer (Spizzo et al., 2006).
Oncogenesis
EpCAM is strongly overexpressed.
Renal cancer (RCC)
Prognosis
Increased expression of EpCAM is a marker for
improved prognosis in patients suffering from clear cell
RCC and might help to discriminate between
chromophobe RCC and oncocytomas (Went et al.,
2005).
Oncogenesis
EpCAM is strongly overexpressed in chromophobe
RCC but not in oncocytomas.
References
Linnenbach AJ, Wojcierowski J, Wu SA, Pyrc JJ, Ross AH,
Dietzschold B, Speicher D, Koprowski H. Sequence
investigation of the major gastrointestinal tumor-associated
antigen family, GA733. Proc Natl Acad Sci USA 1989;86
(1):27-31.
Head and Neck Squamous Cell
carcinomas (HNSCCs)
Prognosis
Expression of EpCAM is a marker for disseminated
tumour cells in HNSCCs (Chaubal et al., 1999).
Oncogenesis
EpCAM is strongly overexpressed in HNSCCS.
Strnad J, Hamilton AE, Beavers LS, Gamboa GC, Apelgren
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Esophagus Squamous Cell carcinomas
Prognosis
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444
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Gires O
Szala S, Froehlich M, Scollon M, Kasai Y, Steplewski Z,
Koprowski H, Linnenbach AJ. Molecular cloning of cDNA for
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Litvinov SV, Balzar M, Winter MJ, Bakker HA, Briaire-de Bruijn
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molecule (Ep-CAM) modulates cell-cell interactions mediated
by classic cadherins. J Cell Biol 1997;139(5):1337-1348.
Schmelzer E, Zhang L, Bruce A, Wauthier E, Ludlow J, Yao
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This article should be referenced as such:
Gires O. TACSTD1 (tumor-associated calcium
transducer
1).
Atlas
Genet
Cytogenet
Haematol.2008;12(6):443-445.
Gastl G, Spizzo G, Obrist P, Dunser M, Mikuz G. Ep-CAM
overexpression in breast cancer as a predictor of survival.
Lancet 2000;356(9246):1981-1982.
Munz M, Kieu C, Mack B, Schmitt B, Zeidler R, Gires O. The
carcinoma-associated antigen EpCAM upregulates c-myc and
induces cell proliferation. Oncogene 2004;23(34):5748-5758.
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445
signal
Oncol