Epithelial cell adhesion molecule
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Epithelial cell adhesion molecule (EpCAM), also known as CD326 among other names, is a
Expression pattern
First discovered in 1979, EpCAM was initially described as a dominant surface antigen on human colon carcinoma.[11] Because of its prevalence on many carcinomas, it has been "discovered" many different times.[12] EpCAM therefore has many aliases the most notable of which include TACSTD1 (tumor-associated calcium signal transducer 1), CD326 (cluster of differentiation 326), and the 17-1A antigen.[13]
EpCAM expression is not limited to human colon carcinomas; in fact, EpCAM is expressed in a variety of human epithelial tissues, carcinomas, and
EpCAM is frequently upregulated in carcinomas but is not expressed in cancers of non-epithelial origin. In cancer cells, EpCAM is expressed in a dispersed pattern across the cell membrane.[14] However, EpCAM expression in carcinomas is often heterogeneous; some cells in a tumor have more EpCAM than other cells in the same tumor.
Squamous carcinomas often express EpCAM whereas normal squamous cells do not express EpCAM. EpCAM expression differs between different types of
Structure
Although it is identified as a cell adhesion molecule, EpCAM does not structurally resemble any of the four major families of
EpCAM is a
Function
The exact function of EpCAM is currently being elucidated, but EpCAM appears to play many different roles.
Cell adhesion
EpCAM was first found to play a role in homotypic cell adhesion.[5] This means that EpCAM on the surface of one cell binds to the EpCAM on a neighboring cell thereby holding the cells together. The adhesions mediated by EpCAM are relatively weak, as compared to some other adhesion molecules, such as classic cadherins.
EpICD is required for EpCAM to mediate intercellular adhesion; EpCAM mediates intercellular adhesion and associates with the actin cytoskeleton via EpICD.[16]
EpCAM has a negative impact on cadherin-mediated adhesions. Overexpression of EpCAM does not alter overall total cellular level of cadherins but rather decreases the association of the cadherin/ catenin complex in the cytoskeleton. As EpCAM expression increases, the total amount of α-catenin decreases, whereas cellular β-catenin levels remain constant.[17]
The homotypic adhesive activity has been questioned, as a variety of in vivo and in vitro biochemical experiments have failed to detect trans-interactions.[18] EpCAM pro-adhesive activity could be explained by alternative models,[19] based on its ability to regulate PKC signalling and myosin activity.[20]
Recently, it has been discovered that EpCAM contributes to the maintenance of tight junctions.[21]
Active proliferation in a number of epithelial tissues is associated with increased or de novo EpCAM expression. This is especially evident in tissues that normally reveal no or low levels of EpCAM expression, such as squamous epithelium. The level of EpCAM expression correlates with the proliferative activity of intestinal cells, and inversely correlates with their differentiation.[8]
Role in cancer
EpCAM can be cleaved which lends the molecule
EpCAM may also play a role in
Clinical significance
Target for immunotherapy
It has been speculated that since EpCAM in normal epithelia is expressed mostly on the basolateral membrane, it would be much less accessible to antibodies than EpCAM in cancer tissue, where it is homogeneously distributed on the cancer cell surface. In addition to being overexpressed in many carcinomas, EpCAM is expressed in cancer stem cells, making EpCAM an attractive target for immunotherapy. However, the heterogeneous expression of EpCAM in carcinomas and the fact that EpCAM is not tumor-specific (i.e., it is found in normal epithelium) raise concerns that immunotherapy directed towards EpCAM could have severe side effects.[13] As the role of EpCAM in cancer cell signaling is better understood, EpCAM signaling rather than EpCAM itself may be a target for therapeutic intervention.[14]
Histopathology
EpCAM is often overexpressed in certain
Genetic disorders
A problem in EpCAM can indirectly cause
Mutations in EpCAM have also been associated with congenital tufting enteropathy[30] which causes intractable diarrhea in newborn children.
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000119888 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000045394 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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- ^ S2CID 13253137.
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External links
- FAQs on HNPCC Archived 15 August 2007 at the National Institute of Health
- GeneReviews/NCBI/NIH/UW entry on Lynch syndrome
- TACSTD1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.