EpCAM Gene Editing    

The epithelial cell adhesion molecule (EpCAM, also known as cluster of differentiation 326 or Tacstd1), is a 40 KD trans-membrane glycoprotein, consisting of 314 amino acids, which is firstly identified in colon cancer in 1979. EpCAM is a homophilic Ca²⁺-independent cell-cell adhesion molecule. In addition to a role in intercellular adhesion, in vitro and in vivo studies have shown that EpCAM plays a significant role in cell signaling, proliferation, differentiation, formation and maintenance of organ morphology.

Figure 1. EpCAM function. (Vasanthakumar S, et al. 2017)

In healthy tissue, high EpCAM levels are associated with proliferation during morphogenesis, tissue regeneration and stem cell maintenance. High EpCAM expression has been found to promote tumor progression in epithelial cancer, and is often associated with poor prognosis. Compared with high EpCAM levels, absence of EpCAM because of gene mutations leads to CTE (congenital tufting enteropathy), a rare disease with severe diarrhea in newborns due to abnormal development of the intestinal epithelium. Due to its tumor-specific overexpression, EpCAM has been explored as a prognostic/diagnostic marker and anti-cancer target since the 1970s.

EpCAM Expression in Cancer

EpCAM is frequently overexpressed in the majority of cancer tissues. On the contrary, the majority of squamous cell carcinomas show lower EpCAM expression than adenocarcinomas and EpCAM was found to be absent in lymphomas, melanomas, sarcomas, and neurogenic tumors. Especially high abundant levels of EpCAM expression can be observed in carcinomas derived from the breast, colon, intestine, lung and prostate. In contrast to healthy epithelia, the distribution of EpCAM varies depending on the type of carcinoma, from a basolateral to a homogenous whole cell membranous distribution. In addition, strong EpCAM signals can also be detected in the cytoplasm and nuclei, because EpCAM is subject to regulated proteolytic cleavage. The prognostic value of EpCAM expression is dependent on the cancer type. In some cancer types (thyroid, renal clear cell, head and neck squamous cell carcinomas), EpCAM immunostaining has been associated with improved survival, whereas in other carcinoma types like pancreas, gall bladder, gastric, bladder, NasoPharynx Carcinoma, EpCAM expression is associated with decreased survival.

EpCAM as a Target in Cancer Therapy

In addition to its prognostic value, EpCAM is an attractive target for tumor diagnosis and therapy due to its tumor-specific overexpression. EpCAM has been used as a target for many immunotherapeutic approaches, including monoclonal antibody therapy and tumor targeted antibody development. Moreover, vaccination strategies, an EpCAM-specific antibody fragment fused to TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand), and toxin-conjugated antibody fragments have been developed. Generally speaking, conjugation of cancer stem cells targeting EpCAM aptamer with a chemotherapeutic drug could transform conventional chemotherapeutic drugs into tumor killers to overcome the drug resistance in tumors. Zheng et al. also found that the EpCAM antibody made chemoresistant myeloid leukemia sensitive to innate immune cells. It has been reported that exosomes in the circulatory system derived from tumors, called extracellular vesicles or vesicles, may easily be isolated using anti-EpCAM antibodies combined with magnetic beads. The exosomes are isolated by a variety of downstream assays such as sandwich immunization assay and RT-qPCR. The isolated exosomes could be used to study the distribution of tumor-specific extracellular body surface proteins and related miRNAs. EpCAM peptide-primed dendritic cell vaccinations exhibit significant anti-tumor immunity in hepatocellular carcinoma cells.

EpCAM Gene Editing Service

CRISPR/Cas9 Platform^CB, one of the leading biotechnological companies specializing in gene editing, is dedicated to offering comprehensive CRISPR/Cas9 gene-editing services to a wide range of genomics researchers. Based on our platform, we can help you effectively EpCAM gene deleted, inserted or point mutated in cells or animals by CRISPR/Cas9 technology.

• EpCAM Gene Knockout: We offer EpCAM gene knockout cell line and knockout animal model generation service with high quality. Typically, we develop CRISPR-mediated gene editing cell lines including HEK239T, Hela, HepG2, U87, but we can use other cell lines according to your requirements. Our one-stop KO animal model generation service covers from sgRNA design and construction, pronuclear microinjection to Founders genotyping and breeding.
• EpCAM Gene Knockin: CRISPR/Cas9 Platform^CB provides the one-stop EpCAM knock-in cell line and knockout animal model generation services, including point mutation and gene insertion. Our expert staff has succeeded in dozens of EpCAM knock-in cell line generation projects, including stem cells, tumor cells and even difficult-to-handle cells. We also have extensive experience in incorporating CRISPR/Cas9 technology into animal models, which have been fully recognized by our clients.

If you have any questions, please feel free to contact us.

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