EpCAM (CD326): From Adhesion Molecule to Transformative Tumor Therapeutic Target—Three Decades of Research Progress

1. Concept

EpCAM (Epithelial Cell Adhesion Molecule), also known as CD326, is a highly evolutionarily conserved member of the human adhesion molecule family, with 82% amino acid sequence homology between humans and mice. As a single-pass type I transmembrane glycoprotein (30–40 kDa), it is encoded by the TACSTD1 gene (located on chromosome 2p21, approximately 1.5 kb in length) and regulated by transcriptional repression—wild-type p53 binds to the fourth intron to suppress TACSTD1 expression.

EpCAM’s structure comprises three functional domains: an extracellular domain (encoded by exons 2–6), a single transmembrane domain (exon 7), and an intracellular domain (exons 8–9). Its expression is tissue-specific: it localizes to tight junctions in all normal epithelial cells (except squamous epithelium) and is absent in connective tissue, hematopoietic cells, brain tissue, and vascular endothelial cells. In tumors, it exhibits differential expression—highly expressed (>90%) in adenocarcinomas (esophageal, gastric, colorectal, prostate, lung, ovarian), moderately expressed in breast cancer (73%) and renal cell carcinoma (51.8%), and weakly expressed in hepatocellular carcinoma (14.9%) and sarcomas (4.8%).

2. Research Frontiers

Recent research on EpCAM has focused on unraveling its dual functional mechanisms and expanding its translational potential. A key frontier is the exploration of its context-dependent roles: while EpCAM mediates calcium-independent homotypic adhesion to inhibit migration, it also disrupts E-cadherin/α-catenin/F-actin complexes to promote tumor metastasis—this duality is under intense investigation to clarify regulatory switches.

Another emerging direction is the development of precision-targeted therapies. Building on approved products like Removab (bispecific anti-EpCAM antibody for malignant ascites) and the CellSearch system (for colorectal cancer metastasis detection), researchers are engineering next-generation agents such as antibody-drug conjugates (ADCs) and chimeric antigen receptor (CAR)-T cells targeting EpCAM. Multi-omics integration (genomics, proteomics, metabolomics) is also advancing, enabling comprehensive analysis of EpCAM’s regulatory networks in tumorigenesis. Additionally, studies on EpCAM’s non-canonical signaling pathways (Wnt/PCP, Wnt/Ca²⁺) are uncovering novel therapeutic vulnerabilities.

3. Research Significance

EpCAM is a pivotal biomarker and therapeutic target for epithelial-derived tumors, with profound implications for cancer research and clinical practice. Its role in regulating cell adhesion, migration, proliferation, and Wnt signaling makes it a central mediator of tumor progression and metastasis. By stabilizing β-catenin in the canonical Wnt pathway, EpCAM activates proto-oncogenes (c-myc, cyclin A/E), accelerating cell cycle progression and driving tumorigenesis.

Clinically, EpCAM’s tissue-specific expression and differential tumor enrichment enable accurate cancer diagnosis and prognosis assessment. Therapeutically, targeting EpCAM has shown promising results in treating advanced tumors and malignant ascites, addressing unmet medical needs. Basic research on EpCAM’s signaling crosstalk also provides insights into fundamental biological processes such as cell polarity, intercellular communication, and epithelial-mesenchymal transition (EMT), advancing our understanding of cancer biology.

4. Related Mechanisms, Research Methods, and Product Applications

4.1 Core Biological Mechanisms

• Cell Adhesion and Migration Regulation: EpCAM mediates calcium-independent homotypic adhesion to maintain epithelial integrity; however, overexpression disrupts E-cadherin complexes and interacts with tight junction proteins (e.g., aquaporins) to promote migration and metastasis.
• Cell Proliferation Promotion: EpCAM upregulates c-myc and cyclin A/E, inducing cell cycle regulators (CDK4, CDC25) to accelerate proliferation.
• Tumorigenic Signaling: Stabilizes β-catenin in the canonical Wnt pathway, activating oncogenic target genes; may also involve non-canonical Wnt pathways (PCP, Ca²⁺) to regulate cell polarity and calcium signaling.
• Expression Regulation: TNF-α downregulates EpCAM via NF-κB-mediated competitive inhibition of p300/CBP.

4.2 Key Research Methods

• Expression Analysis: Flow cytometry, immunohistochemistry (IHC), and Western blot (WB) using EpCAM-specific antibodies to quantify expression in tissues/cells.
• Functional Validation: In vitro (cell lines) and in vivo (xenograft models) studies with EpCAM overexpression/knockdown to assess adhesion, migration, and proliferation.
• Signaling Pathway Analysis: Co-immunoprecipitation (CoIP), luciferase reporter assays, and phosphoproteomics to dissect EpCAM’s interaction with Wnt/β-catenin and other pathways.
• Clinical Translation: Diagnostic platforms (e.g., flow cytometry-based detection) and therapeutic development (ADC, CAR-T) targeting EpCAM.

4.3 Product Support from ANT BIO PTE. LTD.

ANT BIO PTE. LTD. offers a comprehensive portfolio of EpCAM-related reagents through its specialized sub-brands, supporting every stage of research and translation:

• Recombinant Proteins (UA Sub-brand): Human, mouse, and cynomolgus TROP1/EpCAM His-Tagged Proteins (e.g., UA010236, UA010239, UA010257) expressed in HEK293 cells, ideal for antibody development, binding assays, and functional studies.
• Antibodies (Starter Sub-brand): A diverse range of EpCAM/CD326 antibodies, including recombinant rabbit/mouse mAbs (unconjugated or conjugated to Alexa Fluor® 488/700, PE, PerCP-Cy5.5, FITC) for flow cytometry, IHC, WB, and immunofluorescence. Highlights include S-RMab® EpCAM Recombinant Rabbit mAb (S0B2028) and Mouse Anti-Human CD326 Antibodies (S0B1681, S0B1810).
• General Reagents and Kits (Absin Sub-brand): ELISA kits for EpCAM quantification, WB-related reagents (ECL substrates, precast gels), and cell culture media to support sample preparation, detection, and functional assays.
• Custom Services: Antibody conjugation, recombinant protein expression, and assay development to meet specialized research needs (e.g., custom-labeled antibodies for flow cytometry).

5. Brand Mission

ANT BIO PTE. LTD. is dedicated to empowering life science research and clinical innovation through the provision of high-quality, reliable reagents and comprehensive solutions. As a leading provider of life science products, our portfolio spans antibodies, recombinant proteins, kits, and general reagents, with three specialized sub-brands catering to distinct research needs: Absin (general reagents and kits), Starter (antibodies), and UA (recombinant proteins). Our core mission is to accelerate scientific discovery, bridge the gap between basic research and clinical application, and contribute to the advancement of human health by delivering cutting-edge products, professional technical support, and exceptional customer service. We strive to be a trusted partner for researchers and clinicians worldwide, supporting their efforts to unravel cancer biology mysteries and develop novel diagnostics and therapies.

6. Related Product List (With Product Codes)

7. AI Disclaimer

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ANT BIO PTE. LTD. – Empowering Scientific Breakthroughs

At ANTBIO, we are committed to advancing life science research through high-quality, reliable reagents and comprehensive solutions. Our specialized sub-brands (Absin, Starter, UA) cover a full spectrum of research needs, from general reagents and kits to antibodies and recombinant proteins. With a focus on innovation, quality, and customer-centricity, we strive to be your trusted partner in unlocking scientific mysteries and driving medical progress. Explore our product portfolio today and elevate your research to new heights.