Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

EPCAM (tumor-associated calcium signal transducer 1)

Identity

Other namesTACSTD1 (tumor-associated calcium signal transducer 1)
EpCAM
Ep-CAM
CD326
CO17-1A
EGP
EGP40
GA733-2
KSA
Ly74
M1S2
M4S1
MIC18
MK-1
TROP1
hEGP-2
HGNC (Hugo) EPCAM
LocusID (NCBI) 4072
Location 2p21
Location_base_pair Starts at 47596287 and ends at 47614167 bp from pter ( according to hg19-Feb_2009)  [Mapping]

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
HGNC (Hugo)EPCAM   11529
Cards
AtlasTACSTD1ID42459ch2p21
Entrez_Gene (NCBI)EPCAM  4072  epithelial cell adhesion molecule
GeneCards (Weizmann)EPCAM
Ensembl (Hinxton)ENSG00000119888 [Gene_View]  chr2:47596287-47614167 [Contig_View]  EPCAM [Vega]
AceView (NCBI)EPCAM
Genatlas (Paris)EPCAM
WikiGenes4072
SOURCE (Princeton)NM_002354
Genomic and cartography
GoldenPath (UCSC)EPCAM  -  2p21   chr2:47596287-47614167 +  2p21   [Description]    (hg19-Feb_2009)
EnsemblEPCAM - 2p21 [CytoView]
Mapping of homologs : NCBIEPCAM [Mapview]
OMIM185535   613217   613244   
Gene and transcription
Genbank (Entrez)AK026585 AW050533 BC014785 BP262680 CR542259
RefSeq transcript (Entrez)NM_002354
RefSeq genomic (Entrez)AC_000134 NC_000002 NC_018913 NG_012352 NT_022184 NW_001838769 NW_004929300
Consensus coding sequences : CCDS (NCBI)EPCAM
Cluster EST : UnigeneHs.542050 [ NCBI ]
CGAP (NCI)Hs.542050
Alternative Splicing : Fast-db (Paris)GSHG0016450
Alternative Splicing GalleryENSG00000119888
Gene ExpressionEPCAM [ NCBI-GEO ]     EPCAM [ SEEK ]   EPCAM [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP16422 (Uniprot)
NextProtP16422  [Medical]
With graphics : InterProP16422
Splice isoforms : SwissVarP16422 (Swissvar)
Domaine pattern : Prosite (Expaxy)THYROGLOBULIN_1_1 (PS00484)    THYROGLOBULIN_1_2 (PS51162)   
Domains : Interpro (EBI)Thyroglobulin_1   
Related proteins : CluSTrP16422
Domain families : Pfam (Sanger)Thyroglobulin_1 (PF00086)   
Domain families : Pfam (NCBI)pfam00086   
Domain families : Smart (EMBL)TY (SM00211)  
DMDM Disease mutations4072
Blocks (Seattle)P16422
Human Protein AtlasENSG00000119888
Peptide AtlasP16422
HPRD01709
IPIIPI00296215   IPI00893715   IPI00893928   
Protein Interaction databases
DIP (DOE-UCLA)P16422
IntAct (EBI)P16422
FunCoupENSG00000119888
BioGRIDEPCAM
InParanoidP16422
Interologous Interaction database P16422
IntegromeDBEPCAM
STRING (EMBL)EPCAM
Ontologies - Pathways
Ontology : AmiGOureteric bud development  protein binding  plasma membrane  tight junction  positive regulation of cell proliferation  cell surface  integral to membrane  basolateral plasma membrane  apical plasma membrane  lateral plasma membrane  
Ontology : EGO-EBIureteric bud development  protein binding  plasma membrane  tight junction  positive regulation of cell proliferation  cell surface  integral to membrane  basolateral plasma membrane  apical plasma membrane  lateral plasma membrane  
REACTOMEEPCAM
Protein Interaction DatabaseEPCAM
Wikipedia pathwaysEPCAM
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)EPCAM
SNP (GeneSNP Utah)EPCAM
SNP : HGBaseEPCAM
Genetic variants : HAPMAPEPCAM
1000_GenomesEPCAM 
ICGC programENSG00000119888 
Somatic Mutations in Cancer : COSMICEPCAM 
CONAN: Copy Number AnalysisEPCAM 
Mutations and Diseases : HGMDEPCAM
OMIM185535    613217    613244   
GENETestsEPCAM
Disease Genetic AssociationEPCAM
Huge Navigator EPCAM [HugePedia]  EPCAM [HugeCancerGEM]
Genomic VariantsEPCAM  EPCAM [DGVbeta]
Exome VariantEPCAM
dbVarEPCAM
ClinVarEPCAM
snp3D : Map Gene to Disease4072
General knowledge
Homologs : HomoloGeneEPCAM
Homology/Alignments : Family Browser (UCSC)EPCAM
Phylogenetic Trees/Animal Genes : TreeFamEPCAM
Chemical/Protein Interactions : CTD4072
Chemical/Pharm GKB GenePA35493
Clinical trialEPCAM
Cancer Resource (Charite)ENSG00000119888
Other databases
Probes
Litterature
PubMed146 Pubmed reference(s) in Entrez
CoreMineEPCAM
iHOPEPCAM

Bibliography

Sequence investigation of the major gastrointestinal tumor-associated antigen gene family, GA733.
Linnenbach AJ, Wojcierowski J, Wu SA, Pyrc JJ, Ross AH, Dietzschold B, Speicher D, Koprowski H
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
Cancer research. 1990 ; 50 (13) : 4154-4159.
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.
Schn MP, Schn 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, Mller 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
Journal of molecular medicine (Berlin, Germany). 1999 ; 77 (10) : 699-712.
PMID 10606205
 
Ep-CAM overexpression in breast cancer as a predictor of survival.
Gastl G, Spizzo G, Obrist P, Dnser M, Mikuz G
Lancet. 2000 ; 356 (9246) : 1981-1982.
PMID 11130529
 
The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation.
Mnz 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, Andr 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
The Journal of experimental medicine. 2007 ; 204 (8) : 1973-1987.
PMID 17664288
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

Contributor(s)

Written02-2008Olivier 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 . EPCAM (tumor-associated calcium signal transducer 1). Atlas Genet Cytogenet Oncol Haematol. February 2008 .
URL : http://AtlasGeneticsOncology.org/Genes/TACSTD1ID42459ch2p21.html

The various updated versions of this paper are referenced and archived by INIST as such :
http://documents.irevues.inist.fr/bitstream/2042/38601/1/02-2008-TACSTD1ID42459ch2p21.pdf   [ Bibliographic record ]

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Mar 31 08:43:23 CEST 2014

Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.