The EPCAM gene encodes a transmembrane glycoprotein, Epithelial Cell Adhesion Molecule (EPCAM), also known as CD326 or Trop-1, which mediates calcium-independent homotypic cell adhesion and participates in fundamental processes including cell adhesion, migration, proliferation, and signal transduction, thereby maintaining epithelial tissue integrity ^[1]. While normally expressed on the surface of epithelial cells in organs such as the gastrointestinal tract, lungs, and skin, EPCAM is frequently overexpressed in various cancers, including colorectal, breast, and pancreatic carcinomas, but is largely absent or weakly expressed in healthy squamous epithelia ^[1]. Structurally, EPCAM comprises an extracellular domain (EpEX) mediating intercellular adhesion, a transmembrane domain, and a short intracellular domain (EpICD). Upon proteolytic cleavage by ADAM17 and γ-secretase, EpICD translocates to the nucleus, activating oncogenic pathways such as Wnt/β-catenin, ERK, and FAK-AKT, which promotes epithelial-mesenchymal transition (EMT), tumor progression, and metastasis ^[2]. Notably, EPCAM serves as a marker for circulating tumor cells (CTCs) and cancer stem cells, and its downregulation during EMT can complicate advanced cancer detection ^[2-3]. Furthermore, dysregulated EPCAM expression is associated with congenital tufting enteropathy (CTE), a severe intestinal epithelial dysfunction ^[2]. Given its involvement in tumor metastasis through interaction with HGFR (c-Met), targeting EPCAM with strategies like the neutralizing antibody EpAb2-6 in combination with HGFR inhibitors has shown promising preclinical efficacy ^[4].

The B6-huEPCAM mouse is a humanized model constructed through gene-editing technology, in which the mouse Epcam extracellular domain is replaced with the human EPCAM extracellular domain. This model can be used for research on tumor mechanisms and tumor immunotherapy, as well as for the development of EPCAM-targeted drugs.