EPCAM

What is EPCAM Protein?

EPCAM gene (epithelial cell adhesion molecule) is a protein coding gene which situated on the short arm of chromosome 2 at locus 2p21. This gene encodes a carcinoma-associated antigen and is a member of a family that includes at least two type I membrane proteins. This antigen is expressed on most normal epithelial cells and gastrointestinal carcinomas and functions as a homotypic calcium-independent cell adhesion molecule. The antigen is being used as a target for immunotherapy treatment of human carcinomas. The EPCAM protein is consisted of 314 amino acids and EPCAM molecular weight is approximately 34.9 kDa.

What is the Function of EPCAM Protein?

EPCAM is a cell surface glycoprotein that plays a role in a variety of physiological and pathological processes, and it was originally discovered as a tumor antigen. EPCAM is involved in the regulation of intercellular adhesion strength and tissue plasticity, and influences cell proliferation and differentiation. In tissue regeneration and stem cell research, EPCAM helps maintain the stem cell properties of cells. At the molecular level, EPCAM is involved in homologous adhesion between cells through its extracellular domains, while its intracellular domains interact with the cytoskeleton to influence cell morphology and movement. In addition, EPCAM can produce active extracellular and intracellular fragments through controlled endometrial proteolysis, which in turn affects a variety of signal transduction processes including WNT and Ras/Raf signaling pathways.

EPCAM Related Signaling Pathway

The extracellular domain (EpEX) of EpCAM binds to the epidermal growth factor receptor (EGFR) and activates the AKT and MAPK signaling pathways. This can inhibit the function of the transcription factor FOXO3a and stabilize the PD-L1 protein, thus promoting tumor progression. EpCAM produces active extracellular and intracellular fragments through controlled intimal proteolysis (RIP). In particular, the intracellular fragment of EpCAM (EpICD) can be transported to the nucleus, form complexes with β-catenin and Lef-1, promote gene transcription, and is associated with the proliferation of tumor cells. EpCAM regulates Wnt signaling through RIP and influences cell proliferation and cell fate determination. EpCAM participates in intercellular adhesion and influences intercellular interactions by forming autodimers or heterodimers.

Fig1. Schematic of signaling pathways of EpCAM. (Markus Munz, 2009)

EPCAM Related Diseases

EPCAM is a glycoprotein expressed in a variety of epithelial cell and epithelial-derived tumors, and its abnormal expression has been associated with a variety of diseases. It is involved in regulating cell adhesion, proliferation, differentiation, migration and signaling. Studies have shown that EPCAM is abnormally expressed in many human tumors and that its expression levels correlate with disease prognosis, particularly in colorectal, gastric, prostate, and breast cancers. In addition, the role of EPCAM signaling in tumor progression is multifaceted, including promoting tumor cell invasion, immune escape, and activation of downstream oncogenes.

Bioapplications of EPCAM

EPCAM is a known tumor antigen on epithelial tumors, circulating tumor cells and tumor stem cells, and monoclonal antibodies against EPCAM have been used in a variety of cancer therapies. Epcam-car T cell therapy, which uses chimeric antigen receptor modified T cells to target EpCAM, has been shown to be safe and effective in solid tumors in preclinical and clinical studies. As a prognostic marker, therapeutic target and anchor molecule of CTC, EpCAM plays an important role in the detection and analysis of CTC. Antibody drug couplings (ADCs), such as Oportuzumab Monatox and Citatuzumab Bogatox, use EpCAM antibodies to bind to toxins to target cancer cells for precision killing