Epithelial Cell Adhesion Molecule (EPCAM) is a protein found on the surface of cells throughout the body. It plays a part in both the normal functioning of healthy cells and the development of certain diseases, particularly various types of cancer. Understanding EPCAM’s activities provides insights for biological research and holds promise for developing new medical applications.
Understanding EPCAM
EPCAM is a protein that spans the cell membrane, making it a transmembrane glycoprotein. The protein consists of three main parts: a large extracellular domain that extends outside the cell, a transmembrane domain that anchors it within the cell membrane, and a short intracellular domain located inside the cell. EPCAM is primarily located on the surface of epithelial cells, which form the linings of organs, glands, and the skin. In its normal state, EPCAM is thought to form cis-dimers, where two EPCAM molecules on the same cell surface interact. These dimers can further associate into trans-tetramers, which may contribute to cell-to-cell interactions.
Normal Cellular Roles
In healthy tissues, EPCAM contributes to maintaining the structural integrity of epithelial layers. It participates in cell-to-cell adhesion, helping cells stick together and form coherent tissues. Beyond adhesion, EPCAM plays a part in regulating fundamental cellular processes. It is involved in controlling cell proliferation (growth), differentiation (specialization), and migration. EPCAM also has roles in embryonic development and the regeneration of tissues, indicating its broad importance in biological systems.
EPCAM’s Involvement in Cancer
In many cancers, the expression of EPCAM changes significantly, often becoming much higher than in normal cells, observed in a range of epithelial cancers including those affecting the colon, breast, ovaries, lungs, pancreas, and stomach. This increased presence is associated with a more aggressive disease and a less favorable patient outlook. EPCAM contributes to cancer progression by promoting the growth of tumors and enhancing the ability of cancer cells to migrate and invade new tissues, a process known as metastasis. It can also act as a marker for cancer stem cells, which drive tumor growth and resistance to treatment. The protein achieves these effects by influencing various signaling pathways within cancer cells, such as the Wnt pathway and the PI3K/AKT/mTOR pathway, which are known to support cell survival and proliferation.
Clinical Applications of EPCAM
Given its distinctive presence in cancer, EPCAM is a valuable tool in medical settings, serving as a biomarker for cancer diagnosis and predicting disease progression. For example, detecting circulating tumor cells (CTCs) in the bloodstream, which often express EPCAM, can help monitor disease spread and treatment effectiveness. EPCAM is also being explored as a target for new therapies. Antibody-based treatments, such as monoclonal antibodies, are designed to bind to EPCAM on cancer cells. This binding can directly inhibit cancer cells or deliver toxic agents, like in antibody-drug conjugates (ADCs). Bispecific T-cell engagers and CAR-T cell therapies are also being developed to redirect immune cells to recognize and destroy EPCAM-positive cancer cells.