Epithelial cell adhesion molecule (EpCAM) (EpCAM)

Murine EpCAM (Epithelial Cell Adhesion Molecule), also known as CD326 or Tacstd1, is a 40 kDa type I transmembrane glycoprotein primarily expressed on the basolateral membrane of epithelial cells in Mus musculus [1, 2]. It functions as a calcium-independent homophilic cell adhesion molecule and plays a critical role in maintaining epithelial integrity, regulating cell proliferation, and supporting stem cell pluripotency [2, 6, 10]. In the context of disease, EpCAM is significantly overexpressed in various carcinomas, such as colorectal, breast, and lung cancers, and serves as a marker for cancer stem cells and circulating tumor cells [3, 8, 16]. Its signaling is mediated through regulated intramembrane proteolysis (RIP), where the released intracellular domain (EpICD) triggers the Wnt/beta-catenin pathway to promote oncogenesis [6, 12, 15]. Therapeutic strategies targeting EpCAM include monoclonal antibodies, bispecific T-cell engagers (BiTEs), and antibody-drug conjugates [5, 9, 11]. For instance, MuS110 is a murine-specific BiTE antibody used in preclinical research to evaluate the safety and efficacy of T-cell redirection against EpCAM-expressing tumors [5, 9]. While EpCAM is a promising target, therapeutic development faces challenges such as on-target, off-tumor toxicity due to its expression in normal epithelial tissues, particularly the gastrointestinal tract [9, 11]. Additionally, mutations in the EpCAM gene are linked to congenital tufting enteropathy, a severe diarrheal disease [6, 7, 12].

Other names

CD326Tumor-associated calcium signal transducer 1Tacstd1Epithelial glycoprotein 314mEGP314Protein 289ATrop-1Lymphocyte antigen 74mEpCAMmTrop1

T-cell redirection via bispecific antibodies, induction of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), inhibition of oncogenic signaling pathways, and targeted delivery of cytotoxic payloads.