| Written | 2008-02 | Olivier Gires |
| Clinical Cooperation Group Molecular Oncology, Munich Medical Center, Ludwig-Maximilians-University, Marchioninistr. 15, D-81377 Munich, Germany,, HelmholtzZentrum munchen, German Research Center for Environmental Health, Marchioninistr. 25, D-81377 Munich, Germany |
| Identity |
| Alias_names | M4S1 |
| MIC18 | |
| TACSTD1 | |
| antigen identified by monoclonal antibody AUA1 | |
| tumor-associated calcium signal transducer 1 | |
| Alias_symbol (synonym) | Ly74 |
| TROP1 | |
| GA733-2 | |
| EGP34 | |
| EGP40 | |
| EGP-2 | |
| KSA | |
| CD326 | |
| Ep-CAM | |
| HEA125 | |
| KS1/4 | |
| MK-1 | |
| MH99 | |
| MOC31 | |
| 323/A3 | |
| 17-1A | |
| TACST-1 | |
| CO-17A | |
| ESA | |
| Other alias | TACSTD1 (tumor-associated calcium signal transducer 1) |
| EpCAM | |
| CO17-1A | |
| EGP | |
| M1S2 | |
| hEGP-2 | |
| HGNC (Hugo) | EPCAM |
| LocusID (NCBI) | 4072 |
| Atlas_Id | 42459 |
| Location | 2p21 [Link to chromosome band 2p21] |
| Location_base_pair | Starts at 47369148 and ends at 47387028 bp from pter ( according to hg19-Feb_2009) [Mapping EPCAM.png] |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| EPCAM (2p21) / ADAM9 (8p11.22) | EPCAM (2p21) / DLEC1 (3p22.2) | EPCAM (2p21) / GNB1 (1p36.33) | |
| EPCAM (2p21) / HERC3 (4q22.1) | EPCAM (2p21) / MSH2 (2p21) | PCSK1 (5q15) / EPCAM (2p21) | |
| PHRF1 (11p15.5) / EPCAM (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 |
| Note | |
| 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/. |
| Bibliography |
| EpCAM (CD326) finding its role in cancer. |
| Baeuerle PA, Gires O |
| British journal of cancer. 2007 ; 96 (3) : 417-423. |
| PMID 17211480 |
| 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 |
| 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 |
| 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 |
| 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 |
| Ep-CAM overexpression in breast cancer as a predictor of survival. |
| Gastl G, Spizzo G, Obrist P, Dünser M, Mikuz G |
| Lancet. 2000 ; 356 (9246) : 1981-1982. |
| PMID 11130529 |
| Distribution of E-cadherin and Ep-CAM in the human lung during development and after injury. |
| Kasper M, Behrens J, Schuh D, Müller 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 |
| Profiling of the tetraspanin web of human colon cancer cells. |
| Le Naour F, André 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 |
| 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 |
| 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 carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation. |
| Münz M, Kieu C, Mack B, Schmitt B, Zeidler R, Gires O |
| Oncogene. 2004 ; 23 (34) : 5748-5758. |
| PMID 15195135 |
| 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 |
| 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 |
| 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 |
| Carcinoma-associated 38-kD membrane glycoprotein MH 99/KS 1/4 is related to proliferation and age of transformed epithelial cell lines. |
| Schön MP, Schön M, Klein CE, Blume U, Bisson S, Orfanos CE |
| The Journal of investigative dermatology. 1994 ; 102 (6) : 987-991. |
| PMID 8006466 |
| 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 |
| 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 |
| 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 |
| Citation |
| This paper should be referenced as such : |
| Gires, O |
| TACSTD1 (tumor-associated calcium signal transducer 1) |
| Atlas Genet Cytogenet Oncol Haematol. 2008;12(6):443-445. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/TACSTD1ID42459ch2p21.html |
| Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ] |
|
t(2;3)(p21;p22) EPCAM/DLEC1
|
| Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 1 ] |
| Lynch Syndrome |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Nov 13 22:03:49 CET 2019 |
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