TACSTD1 (tumor-associated calcium signal transducer 1)

Identity

Other names	EpCAM
	Ep-CAM
	CD326
	CO17-1A
	EGP
	EGP40
	GA733-2
	KSA
	Ly74
	M1S2
	M4S1
	MIC18
	MK-1
	TROP1
	hEGP-2
Hugo	TACSTD1
Location	2p21

DNA/RNA

Description	The gene is composed of 9 exons and encompasses.
Transcription	1.528kb mRNA; 945bp open reading frame from base pairs 179 to 1123, (NM_002354).
Pseudogene	No pseudogene described so far.

Protein

Description	314 amino acids (aa); 265 aa extracellular domain, 23 aa transmembrane domain, 26 aa intracellular domain; 34-42kDa 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).
Localisation	Plasma membrane; baso-lateral in normal cells; redistribution on entire plasma membrane in vitro and in carcinoma cells.
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 c-myc 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)(Riethmuller et al. 1994)(Schweizer et al. 2002)(Amann et al. 2008)(Ruf et al. 2007).
Homology	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/GA733-1), especially in the extracellular domain including cystein-rich EGF-like domains, conserved region similar to thyroglobulin type I repeat (Thyr I-like repeat).

Mutations

Note	So far, no mutations of the TACSTD1/epcam gene were described.

Implicated in

Entity	Colon cancer
Oncogenesis	EpCAM is strongly overexpressed and was used as a molecular target for monoclonal, therapeutic antibody 17-1A (Panorex ©)(Riethmuller et al.1994) EpCAM, in a complex with claudin-7, CD44 isoforms, and tetraspanins, is involved in colorectal cancer progression (Kuhn et al. 2007).
Entity	Breast cancer
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.
Entity	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.
Entity	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.
Entity	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.
Entity	Esophagus Squamous Cell carcinomas
Prognosis	Increased expression of EpCAM is a marker for decreased relapse-free survival (Stoecklein et al. 2006).
Oncogenesis	EpCAM is strongly overexpressed.
Entity	Hepatocyte development
Note	EpCAM is strongly expressed in differentiation hepatocytes and progenitors thereof (Schmelzer et al. 2007) (Schmelzer and Reid, 2008).

Breakpoints

Note	No breakpoints described so far.

To be noted

The gene name TACSTD1, for Tumour-Associated 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.epcam-symposium.de/.

External links

	Nomenclature
Hugo	TACSTD1
GDB	TACSTD1
Entrez_Gene	TACSTD1  4072  tumor-associated calcium signal transducer 1
	Cards
Atlas	TACSTD1ID42459ch2p21
GeneCards	TACSTD1
Ensembl	TACSTD1 [Search_View]   ENSG00000119888 [Gene_View]
Genatlas	TACSTD1
GeneLynx	TACSTD1
eGenome	TACSTD1
euGene	4072
	Genomic and cartography
GoldenPath	TACSTD1  -  2p21   chr2:47449971-47467661 +  2p21   [Description]    (hg18-Mar_2006)
Ensembl	TACSTD1 - 2p21 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	TACSTD1
	Gene and transcription
Genbank	AK026585 [ ENTREZ ]
Genbank	BC014785 [ ENTREZ ]
Genbank	CR542259 [ ENTREZ ]
Genbank	CR542283 [ ENTREZ ]
Genbank	CR593061 [ ENTREZ ]
RefSeq	NM_002354 [ SRS ]    NM_002354 [ ENTREZ ]
RefSeq	AC_000045 [ SRS ]    AC_000045 [ ENTREZ ]
RefSeq	NC_000002 [ SRS ]    NC_000002 [ ENTREZ ]
RefSeq	NT_022184 [ SRS ]    NT_022184 [ ENTREZ ]
RefSeq	NW_927719 [ SRS ]    NW_927719 [ ENTREZ ]
AceView	TACSTD1 AceView - NCBI
Unigene	Hs.699160 [ SRS ]    Hs.699160 [ NCBI ]     HS699160 [ spliceNest ]
Fast-db	18037 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P16422 [ SRS]    P16422 [ EXPASY ]     P16422 [ INTERPRO ]
Prosite	PS00484 THYROGLOBULIN_1_1 [ SRS ]    PS00484 THYROGLOBULIN_1_1 [ Expasy ]
Prosite	PS51162 THYROGLOBULIN_1_2 [ SRS ]    PS51162 THYROGLOBULIN_1_2 [ Expasy ]
Interpro	IPR000716 Thyroglobulin_1 [ SRS ]    IPR000716 Thyroglobulin_1 [ EBI ]
CluSTr	P16422
Pfam	PF00086 Thyroglobulin_1 [ SRS ]    PF00086 Thyroglobulin_1 [ Sanger ]    pfam00086 [ NCBI-CDD ]
Smart	SM00211 TY [EMBL]
Blocks	P16422
HPRD	01709
	Protein Interaction databases
DIP	P16422
IntAct	P16422
	Polymorphism : SNP, mutations, diseases
OMIM	185535    [ map ]
GENECLINICS	185535
SNP	TACSTD1 [dbSNP-NCBI]
SNP	NM_002354 [SNP-NCI]
SNP	TACSTD1 [GeneSNPs - Utah]  TACSTD1] [HGBASE - SRS]
HAPMAP	TACSTD1 [HAPMAP]
HGMD	TACSTD1
	General knowledge
Family Browser	TACSTD1 [UCSC Family Browser]
SOURCE	NM_002354
SMD	Hs.699160
SAGE	Hs.699160
GO	plasma membrane [Amigo]  plasma membrane
GO	integral to membrane [Amigo]  integral to membrane
PubGene	TACSTD1
TreeFam	TACSTD1
CTD	4072 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	TACSTD1 Related clones (RZPD - Berlin)
	PubMed
PubMed	40 Pubmed reference(s) in LocusLink

Bibliography

Sequence investigation of the major gastrointestinal tumor-associated antigen gene family, GA733.

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Proceedings of the National Academy of Sciences of the United States of America. 1989 ; 86 (1) : 27-31.

PMID 2911574

Molecular cloning and characterization of a human adenocarcinoma/epithelial cell surface antigen complementary DNA.

Strnad J, Hamilton AE, Beavers LS, Gamboa GC, Apelgren LD, Taber LD, Sportsman JR, Bumol TF, Sharp JD, Gadski RA

Cancer research. 1989 ; 49 (2) : 314-317.

PMID 2463074

Phase I clinical comparative study of monoclonal antibody KS1/4 and KS1/4-methotrexate immunconjugate in patients with non-small cell lung carcinoma.

Elias DJ, Hirschowitz L, Kline LE, Kroener JF, Dillman RO, Walker LE, Robb JA, Timms RM

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PMID 2162255

Molecular cloning of cDNA for the carcinoma-associated antigen GA733-2.

Szala S, Froehlich M, Scollon M, Kasai Y, Steplewski Z, Koprowski H, Linnenbach AJ

Proceedings of the National Academy of Sciences of the United States of America. 1990 ; 87 (9) : 3542-3546.

PMID 2333300

Ep-CAM: a human epithelial antigen is a homophilic cell-cell adhesion molecule.

Litvinov SV, Velders MP, Bakker HA, Fleuren GJ, Warnaar SO

The Journal of cell biology. 1994 ; 125 (2) : 437-446.

PMID 8163559

Carcinoma-associated 38-kD membrane glycoprotein MH 99/KS 1/4 is related to proliferation and age of transformed epithelial cell lines.

Schˆn MP, Schˆn M, Klein CE, Blume U, Bisson S, Orfanos CE

The Journal of investigative dermatology. 1994 ; 102 (6) : 987-991.

PMID 8006466

E-cadherin, NCAM, and EpCAM expression in human fetal pancreata.

Cirulli V, Ricordi C, Hayek A

Transplantation proceedings. 1995 ; 27 (6) : page 3335.

PMID 8539977

Distribution of E-cadherin and Ep-CAM in the human lung during development and after injury.

Kasper M, Behrens J, Schuh D, Mˆșller M

Histochemistry and cell biology. 1995 ; 103 (4) : 281-286.

PMID 7648403

Reduction of EGP-2-positive pulmonary metastases by bispecific-antibody-redirected T cells in an immunocompetent rat model.

Kroesen BJ, Helfrich W, Bakker A, Wubbena AS, Bakker H, Kal HB, The TH, de Leij L

International journal of cancer. Journal international du cancer. 1995 ; 61 (6) : 812-818.

PMID 7790116

Epithelial cell adhesion molecule (Ep-CAM) modulates cell-cell interactions mediated by classic cadherins.

Litvinov SV, Balzar M, Winter MJ, Bakker HA, Briaire-de Bruijn IH, Prins F, Fleuren GJ, Warnaar SO

The Journal of cell biology. 1997 ; 139 (5) : 1337-1348.

PMID 9382878

The biology of the 17-1A antigen (Ep-CAM).

Balzar M, Winter MJ, de Boer CJ, Litvinov SV

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PMID 10606205

Ep-CAM overexpression in breast cancer as a predictor of survival.

Gastl G, Spizzo G, Obrist P, Dˆșnser M, Mikuz G

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PMID 11130529

The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation.

Mˆșnz M, Kieu C, Mack B, Schmitt B, Zeidler R, Gires O

Oncogene. 2004 ; 23 (34) : 5748-5758.

PMID 15195135

EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy.

Osta WA, Chen Y, Mikhitarian K, Mitas M, Salem M, Hannun YA, Cole DJ, Gillanders WE

Cancer research. 2004 ; 64 (16) : 5818-5824.

PMID 15313925

Profiling of the tetraspanin web of human colon cancer cells.

Le Naour F, Andrˆ© M, Greco C, Billard M, Sordat B, Emile JF, Lanza F, Boucheix C, Rubinstein E

Molecular & cellular proteomics : MCP. 2006 ; 5 (5) : 845-857.

PMID 16467180

EpCAM (CD326) finding its role in cancer.

Baeuerle PA, Gires O

British journal of cancer. 2007 ; 96 (3) : 417-423.

PMID 17211480

Phenotypic characterization of human colorectal cancer stem cells.

Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, Hoey T, Gurney A, Huang EH, Simeone DM, Shelton AA, Parmiani G, Castelli C, Clarke MF

Proceedings of the National Academy of Sciences of the United States of America. 2007 ; 104 (24) : 10158-10163.

PMID 17548814

Isolation of rare circulating tumour cells in cancer patients by microchip technology.

Nagrath S, Sequist LV, Maheswaran S, Bell DW, Irimia D, Ulkus L, Smith MR, Kwak EL, Digumarthy S, Muzikansky A, Ryan P, Balis UJ, Tompkins RG, Haber DA, Toner M

Nature. 2007 ; 450 (7173) : 1235-1239.

PMID 18097410

Identification and expansion of human colon-cancer-initiating cells.

Ricci-Vitiani L, Lombardi DG, Pilozzi E, Biffoni M, Todaro M, Peschle C, De Maria R

Nature. 2007 ; 445 (7123) : 111-115.

PMID 17122771

Human hepatic stem cells from fetal and postnatal donors.

Schmelzer E, Zhang L, Bruce A, Wauthier E, Ludlow J, Yao HL, Moss N, Melhem A, McClelland R, Turner W, Kulik M, Sherwood S, Tallheden T, Cheng N, Furth ME, Reid LM

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PMID 17664288

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Contributor(s)

Written	02-2008	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

Citation

This paper should be referenced as such :

Gires O . TACSTD1 (tumor-associated calcium signal transducer 1). Atlas Genet Cytogenet Oncol Haematol. February 2008 . URL : http://AtlasGeneticsOncology.org/Genes/TACSTD1ID42459ch2p21.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Wed Jul 2 08:27:23 2008