EPCAM (Epithelial Cell Adhesion Molecule) is a Protein Coding gene. Diseases associated with EPCAM include Diarrhea 5, With Tufting Enteropathy, Congenital and Colorectal Cancer, Hereditary Nonpolyposis, Type 8. Among its related pathways are Cytoskeletal Signaling and Cell surface interactions at the vascular wall. An important paralog of this gene is TACSTD2.
EpCAM can be cleaved which lends the molecule oncogenic potential. Upon cleavage, the extracellular domain (EpEX) is released into the area surrounding the cell, and the intracellular domain (EpICD) is released into the cytoplasm of the cell. EpICD forms a complex with the proteins FHL2, β-catenin, and Lef inside the nucleus. This complex then binds to DNA and promotes the transcription of various genes. Targets of upregulation include c-myc, e-fabp, and cyclins A & E. This has the effect of promoting tumor growth. Additionally, EpEX that has been cleaved can stimulate the cleavage of additional EpCAM molecules resulting in a positive feedback loop. The amount of β-catenin in the nucleus can modulate the expression level of EpCAM.
EpCAM may also play a role in epithelial mesenchymal transition (EMT) in tumors, although its exact effects are poorly understood. Its ability to suppress E-cadherin suggests that EpCAM would promote EMT and tumor metastasis, but its homotypic cell adhesion properties can counteract its ability to suppress E-cadherin. Results from different studies are often conflicting. In one study, for example, silencing of EpCAM with short interfering RNA (siRNA) led to a reduction of proliferation, migration, and invasion of breast cancer cells in vitro supporting the role of EpCAM in promoting EMT.