Epithelial cell adhesion molecule ( Eng. Epithelial cell adhesion molecule; EpCAM , CD326) - membrane protein , cell adhesion molecule . It mediates Ca 2+ -independent intercellular adhesion in the epithelium . [1] EpCAM is involved in signal transduction, [2] cell migration, [3] proliferation and differentiation. [four]
| Epithelial cell adhesion molecule | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| |||||||||||||
| Identifiers | |||||||||||||
| , DIAR5, EGP-2, EGP314, EGP40, ESA, HNPCC8, KS1 / 4, KSA, M4S1, MIC18, MK-1, TACSTD1, TROP1, epithelial cell adhesion molecule | |||||||||||||
| External IDs | |||||||||||||
| |||||||||||||
| RNA expression profile | |||||||||||||
 | |||||||||||||
| Orthologists | |||||||||||||
| Kinds | Person | Mouse | |||||||||||
| Entrez | |||||||||||||
| Ensembl | |||||||||||||
| Uniprot | |||||||||||||
| RefSeq (mRNA) | |||||||||||||
| RefSeq (protein) | |||||||||||||
| Locus (UCSC) | |||||||||||||
| PubMed Search | |||||||||||||
| Wikidata | |||||||||||||
| View / Edit (Man) | View / Edit (Mouse) | ||||||||||||
In addition, EpCAM has oncogenic potential because it can enhance the effect of factors such as c-myc , e-fabp, and cyclins A and E. [5] Due to the specific expression of the protein exclusively in epithelium and tumors of epithelial origin, EpCAM can serve as a marker different types of cancer. It plays a role in the development of tumors, metastasis of carcinoma. [6]
Tissue expression
The protein was discovered for the first time in 1979 as the dominant surface antigen of human colon carcinoma. [7] Since it is widely represented on many carcinomas, it subsequently reopened many times [8] , each time receiving new names. This explains the large number of EpCAM synonyms: TACSTD1, CD326, antigen 17-1A, etc. [9]
EpCAM expression is not limited to colon carcinoma; it is present in a number of human epithelial tissues, carcinomas, progenitor cells, and stem cells . It is absent on non-epithelial tissues and malignant tumors of non-epithelial origin. Under physiological conditions, EpCAM is localized on the basolateral membrane of all types of endothelium, and the level of expression can vary significantly. However, the protein is absent on squamous epithelial cells. So, in the gastrointestinal tract, the lowest expression of EpCAM is found in the stomach, the small intestine is characterized by an average level of expression, and the large intestine is high. [9]
Structure
Although the protein is functionally classified as a cell adhesion molecule, structurally it has nothing to do with other families of cell adhesion molecules, namely cadherins , integrins , selectins and members of the immunoglobulin superfamily. [9]
EpCAM is a type I transmembrane glycoprotein, molecular weight 30-40 kDa. The protein consists of 314 amino acids and includes one extracellular domain (242 amino acids) with EGF - and thyroglobulin-like repeats, a transmembrane region (23 amino acids) and a short cytosolic domain (26 amino acids). [6]
Functions
Cell adhesion
EpCAM plays a role in homotypic cell adhesion [1] , interacting with the same molecule on a neighboring cell, which ensures intercellular binding due to the extracellular domains of two EpCAM molecules [10] . However, the intercellular contacts mediated by EpCAM are relatively weak compared to the contacts provided by other cell adhesion molecules, such as, for example, cadherins .
EpCAM , on the other hand, has a negative effect on cadherin-mediated cell interaction. When EpCAM is overexpressed, this protein, although it does not affect the overall cadherin level in the cell, weakens the association of cadherin with the catenin complex in the cytoskeleton. Increased expression of EpCAM reduces α-catenin. [11] Active proliferation in epithelial tissue is accompanied by an increase in EpCAM synthesis, while cellular differentiation of epithelial cells is accompanied by a decrease. [four]
Role in Oncology
Partial proteolysis of EpCAM releases the extracellular domain into the intracellular medium, while the intracellular region is released into the cytoplasm, then forms a complex with the FHL2 , β-catenin and Lef proteins inside the nucleus. The resulting protein complex binds to DNA and activates transcription. In this case, the targets of the protein are c-myc , e-fabp and cyclins A and E. [2] This enhances the growth of tumor cells.
Notes
- ↑ 1 2 Litvinov, Sergey et al. Ep-CAM: a human epithelial antigen is a homophilic cell – cell adhesion molecule (Eng.) // The Journal of Cell Biology : journal. - 1994. - Vol. 125 , no. 2 . - P. 437-446 . - DOI : 10.1083 / jcb.125.2.437 . - PMID 8163559 .
- ↑ 1 2 Maetzel, Dorothea et al. Nuclear signalling by tumor-associated antigen EpCAM (Eng.) // Nature Cell Biology : journal. - 2009. - Vol. 11 , no. 2 . - P. 162-171 . - DOI : 10.1038 / ncb1824 . - PMID 19136966 .
- ↑ Osta, WA et al. EpCAM is overexpressed in breast cancer and is a potential target for breast cancer gene therapy (English) // Cancer Research : journal. - American Association for Cancer Research 2004. - Vol. 64 , no. 16 . - P. 5818-5824 . - DOI : 10.1158 / 0008-5472.CAN-04-0754 . - PMID 15313925 .
- ↑ 1 2 Litvinov, Sergey et al. Expression of Ep-CAM in cervical squamous epithelia correlates with an increased proliferation and the disappearance of markers for terminal differentiation (English) // Am J Pathol : journal. - 1996. - Vol. 148 , no. 3 . - P. 865-875 . - PMID 8774141 .
- ↑ Munz, M. et al. The carcinoma-associated antigen EpCAM upregulates c-myc and induces cell proliferation (English) // Oncogene : journal. - 2004. - Vol. 23 , no. 34 . - P. 5748-5758 . - DOI : 10.1038 / sj.onc.1207610 . - PMID 15195135 .
- ↑ 1 2 Armstrong, Andrew; Stephen Eck. EpCAM: a new therapeutic target for an old cancer antigen (Eng.) // Cancer biology & therapy: journal. - 2003. - Vol. 2 , no. 4 . - P. 320—326 . - DOI : 10.4161 / cbt.2.4.451 . - PMID 14508099 .
- ↑ Herlyn, D. et al. Monoclonal antibodies in cell-mediated cytotoxicity against human melanoma and colorectal carcinoma (English) // Eur J Immunol : journal. - 1979. - Vol. 9 , no. 8 . - P. 657-659 . - DOI : 10.1002 / eji.1830090817 . - PMID 499332 .
- ↑ Baeuerle, PA; Gires O. EpCAM (CD326) finding its role in cancer (English) // Br J Cancer : journal. - 2007. - Vol. 96 , no. 3 . - P. 417-423 . - DOI : 10.1038 / sj.bjc.6603494 . - PMID 17211480 .
- ↑ 1 2 3 Balzar, M; Winter MJ; de Boer CJ; Litvinov SV The biology of the 17-1A antigen (Ep-CAM) (neopr.) // J. Mol. Med. - 1999. - October ( t. 77 , No. 10 ). - S. 699-712 . - DOI : 10.1007 / s001099900038 . - PMID 10606205 .
- ↑ Balzar, M; Bakker HA; Briaire-de-Bruijn IH; Fleuren GJ; Warnaar SO; Litvinov SV Cytoplasmic tail regulates the intercellular adhesion function of the epithelial cell adhesion molecule (Eng.) // Mol Cell Biol : journal. - 1998. - Vol. 18 , no. 8 . - P. 4833-4843 . - PMID 9671492 .
- ↑ Litvinov, S. et al. Epithelial cell adhesion molecule (Ep-CAM) modulates cell – cell interactions mediated by classic cadherins (Eng.) // J Cell Biol : journal. - 1997. - Vol. 139 , no. 5 . - P. 1337-1348 . - DOI : 10.1083 / jcb.139.5.1337 . - PMID 9382878 .
Links
- Chapter 18. Molecules of adhesion. Molecule of epithelial cell adhesion, p. 854. . BioChemMac. Date of treatment July 20, 2018.