EPCAM (tumor-associated calcium signal transducer 1)

2008-02-01   Olivier Gires 

Identity

HGNC
LOCATION
2p21
LOCUSID
ALIAS
DIAR5,EGP-2,EGP314,EGP40,ESA,HNPCC8,KS1/4,KSA,M4S1,MIC18,MK-1,TACSTD1,TROP1
FUSION GENES

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.

Proteins

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 name
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 name
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 name
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 name
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 name
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 name
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 name
Hepatocyte development
Note
EpCAM is strongly expressed in differentiation hepatocytes and progenitors thereof (Schmelzer et al. 2007) (Schmelzer and Reid, 2008).

Bibliography

Pubmed IDLast YearTitleAuthors
172114802007EpCAM (CD326) finding its role in cancer.Baeuerle PA et al
106062051999The biology of the 17-1A antigen (Ep-CAM).Balzar M et al
85399771995E-cadherin, NCAM, and EpCAM expression in human fetal pancreata.Cirulli V et al
175488142007Phenotypic characterization of human colorectal cancer stem cells.Dalerba P et al
21622551990Phase I clinical comparative study of monoclonal antibody KS1/4 and KS1/4-methotrexate immunconjugate in patients with non-small cell lung carcinoma.Elias DJ et al
111305292000Ep-CAM overexpression in breast cancer as a predictor of survival.Gastl G et al
76484031995Distribution of E-cadherin and Ep-CAM in the human lung during development and after injury.Kasper M et al
77901161995Reduction of EGP-2-positive pulmonary metastases by bispecific-antibody-redirected T cells in an immunocompetent rat model.Kroesen BJ et al
164671802006Profiling of the tetraspanin web of human colon cancer cells.Le Naour F et al
29115741989Sequence investigation of the major gastrointestinal tumor-associated antigen gene family, GA733.Linnenbach AJ et al
93828781997Epithelial cell adhesion molecule (Ep-CAM) modulates cell-cell interactions mediated by classic cadherins.Litvinov SV et al
151951352004The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation.Münz M et al
180974102007Isolation of rare circulating tumour cells in cancer patients by microchip technology.Nagrath S et al
153139252004EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy.Osta WA et al
171227712007Identification and expansion of human colon-cancer-initiating cells.Ricci-Vitiani L et al
80064661994Carcinoma-associated 38-kD membrane glycoprotein MH 99/KS 1/4 is related to proliferation and age of transformed epithelial cell lines.Schön MP et al
176642882007Human hepatic stem cells from fetal and postnatal donors.Schmelzer E et al
24630741989Molecular cloning and characterization of a human adenocarcinoma/epithelial cell surface antigen complementary DNA.Strnad J et al
23333001990Molecular cloning of cDNA for the carcinoma-associated antigen GA733-2.Szala S et al

Other Information

Locus ID:

NCBI: 4072
MIM: 185535
HGNC: 11529
Ensembl: ENSG00000119888

Variants:

dbSNP: 4072
ClinVar: 4072
TCGA: ENSG00000119888
COSMIC: EPCAM

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000119888ENST00000263735P16422
ENSG00000119888ENST00000405271B5MCA4
ENSG00000119888ENST00000419334C9JKY3
ENSG00000119888ENST00000456133B5MCA4

Expression (GTEx)

0
50
100
150
200
250
300
350

Pathways

PathwaySourceExternal ID
HemostasisREACTOMER-HSA-109582
Cell surface interactions at the vascular wallREACTOMER-HSA-202733

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
191503502009EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features.399
191369662009Nuclear signalling by tumour-associated antigen EpCAM.257
191369662009Nuclear signalling by tumour-associated antigen EpCAM.257
183166092008EpCAM and alpha-fetoprotein expression defines novel prognostic subtypes of hepatocellular carcinoma.238
195856542009Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells.200
195842712009The emerging role of EpCAM in cancer and stem cell signaling.192
190989122009Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1.189
190989122009Heritable somatic methylation and inactivation of MSH2 in families with Lynch syndrome due to deletion of the 3' exons of TACSTD1.189
180068282007Activation of hepatic stem cell marker EpCAM by Wnt-beta-catenin signaling in hepatocellular carcinoma.152
232302782013Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids.125

Citation

Olivier Gires

EPCAM (tumor-associated calcium signal transducer 1)

Atlas Genet Cytogenet Oncol Haematol. 2008-02-01

Online version: http://atlasgeneticsoncology.org/gene/42459/epcam