EpCAM (Epithelial cell adhesion molecule) is a glycosylated, 30- to 40-kDa type I transmembrane protein, that serves important roles in cell adhesion, cell proliferation, differentiation, migration, cell cycle regulation and is implicated in cancer and stem cell signaling. In mammals, EpCAM is predominantly located in intercellular spaces where epithelial cells form very tight junctions. Expression of EpCAM is usually down-regulated as epithelial cells terminally differentiate. However, EpCAM levels often rise again during regeneration or neoplastic transformations. EpCAM is comprised of an extracellular domain with epidermal growth factor (EGF)- and thyroglobulin repeat-like domains, a single transmembrane domain, and a short 26-amino acid intracellular domain called EpICD. The cleavage of the EpCAM ectodomain, EpEx, by TACE the protease (Tumor necrosis factor a converting enzyme) and its shedding has been shown to release its intracellular domain (Ep-ICD) which then translocates to the nucleus resulting in activation of oncogenic signaling. The association of Ep-ICD with FHL2 and Wnt pathway components Beta-catenin and Lef-1 forms a nuclear complex that binds DNA at Lef-1 consensus sites and induces gene transcription, leading to increased cell proliferation (Ralhan R, et al 2010 and Gostner JM, et al 2011). EpCAM acts as a homophilic cell-cell adhesion molecule with positive effects on cell adhesiveness and negative effects on cell motility and metastasis. EpCAM and its partner E-cadherin, promotes both epithelial integrity and epithelial morphogenesis (Slanchev K, et al 2009).

EpCAM is one of the most widely investigated proteins in human cancers, frequently over expressed in human malignancies, localized on the plasma membrane of tumor cells and albeit at lower levels in the normal epithelia. Strikingly, EpCAM is only found in epithelial-derived cancers, i.e., carcinomas, but not in others, such as sarcomas, melanomas, or lymphomas. EpCAM plays a wide role in variety of epithelial cancers, namely, breast, prostate, head and neck, esophagus, ovary, pancreas, colon and rectum, lung, urinary bladder and liver carcinomas (Ralhan R, et al 2010). Numerous reports on the cell surface expression of EpCAM in human cancers have suggested that it could be an ideal candidate for application as an epithelial cancer marker and a therapeutic target. Overexpression of EpCAM reduces the invasive ability of cancer cells which supports the hypothesis that loss of EpCAM expression may be involved in cancer metastasis. Despite over expression of EpCAM occurs in many cancer cells; its role in tumor progression is still a matter of question. The function of EpCAM may depend on biological conditions of tumor microenvironment and its role in cancer could be in a tissue or cell-specific manner (Belov L, et al 2010). The new insights into membrane protein complexes containing EpCAM may be the key to understand both the control of EpCAM signaling in normal vs tumor tissue and the basis for a therapeutic window of some but not all EpCAM-directed immunotherapies. Certain antibody epitopes on EpCAM may only become accessible when accessory proteins are reduced on malignant cells or when EpCAM upon high-level overexpression outnumbers its protein partners. Subsequent oligomerisation of EpCAM may then provide a constitutive proliferation signal for tumor cells (Baeuerle PA, etal 2007 and Munz M, et al 2009).