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Human adeno and squamous cell carcinoma so far reported to show a significant correlation of EpCAM expression with survival prognosis
Source publication
Although epithelial cell adhesion/activating molecule (EpCAM/CD326) is one of the first tumour-associated antigens identified, it has never received the same level of attention as other target proteins for therapy of cancer. It is also striking that ever since its discovery in the late 1970s the actual contribution of EpCAM to carcinogenesis remain...
Citations
... Cancers continue to produce proliferative signals, avoid growth inhibitors, resist cellular death, permit replicative immortality, stimulate angiogenesis, and initiate invasion and metastasis [166]. Widely utilized cancer biomarkers include EpCAM and programmed death-ligand 1 (PD-L1), for which there are small-molecule agents and antibodies available [167][168][169][170][171]. CD47 is required for immune evasion and escape when overexpressed in cancer cells [172]. ...
The emerging strategy of biomimetic nanoparticles (NPs) via cellular membrane camouflage holds great promise in cancer therapy. This scholarly review explores the utilization of cellular membranes derived from diverse cellular entities; blood cells, immune cells, cancer cells, stem cells, and bacterial cells as examples of NP coatings. The camouflaging strategy endows NPs with nuanced tumor-targeting abilities such as self-recognition, homo-typic targeting, and long-lasting circulation, thus also improving tumor therapy efficacy overall. The comprehensive examination encompasses a variety of cell membrane camouflaged NPs (CMCNPs), elucidating their underlying targeted therapy mechanisms and delineating diverse strategies for anti-cancer applications. Furthermore, the review systematically presents the synthesis of source materials and methodologies employed in order to construct and characterize these CMCNPs, with a specific emphasis on their use in cancer treatment.
... The TSPAN8, TSPAN29, and TSPAN30 genes were highly expressed in the primary CRC tissues, with a TPM average exceeding 1 standard deviation from the overall average (Fig. 1A). The TSPAN8, TSPAN29, and TSPAN30 genes had expression levels comparable to the EPCAM gene for the "epithelial cellular adhesion molecule" (EpCAM) protein which is a well-known cell surface tumor marker of epithelial origins (Fig. 1A) (Baeuerle and Gires, 2007). Interestingly, the TSPAN8 gene and CMS3 were clustered on the heatmap's left side (Fig. 1A). ...
... Initially, EpCAM was found ubiquitously and strongly expressed on the surface of various epithelial cancer cells, in particular in prostate, pancreatic, and colorectal cancers [6]. Given its high expression level and immunogenicity, EpCAM is considered as a surface biomarker and potential therapeutic target in human cancers [7]. ...
... The observation of EpCAM-mediated resistance to radiotherapy and chemotherapy suggests the potential of targeted EpCAM immunotherapy in cancer treatment. The efficacy and safety of early anti-EpCAM mAbs (e.g., adecatumumab and edrecolomab) have not been as desired clinically, leading to the development of bispecific antibodies (BsAbs) [7]. Among these, catumaxomab is the world's first trifunctional bispecific antibody (Triomab) approved for the treatment of malignant ascites. ...
The epithelial cell adhesion molecule (EpCAM) is a single transmembrane protein on the cell surface. Given its strong expression on epithelial cells and epithelial cell-derived tumors, EpCAM has been identified as a biomarker for circulating tumor cells (CTCs) and exosomes and a target for cancer therapy. As a cell adhesion molecule, EpCAM has a crystal structure that indicates that it forms a cis-dimer first and then probably a trans-tetramer to mediate intercellular adhesion. Through regulated intramembrane proteolysis (RIP), EpCAM and its proteolytic fragments are also able to regulate multiple signaling pathways, Wnt signaling in particular. Although great progress has been made, increasingly more findings have revealed the context-specific expression and function patterns of EpCAM and their regulation processes, which necessitates further studies to determine the structure, function, and expression of EpCAM under both physiological and pathological conditions, broadening its application in basic and translational cancer research.
... EpCAM was once thought to serve solely as a cell surface and adhesion molecule; however, in recent years, additional evidence of its role in proliferation, cancer progression and decreased survival in cancer patients has emerged [49][50][51]. Signalling commences when EpCAM is cleaved by metalloprotease tumor necrosis factor-alpha converting enzyme, which releases the intracellular domain that then interacts with components of the Wnt pathway and translocates into the nucleus, where it acts as a regulator of transcription for genes that regulate proliferation and the cell cycle [52]. ...
Castration-resistant prostate cancer remains a significant clinical challenge, wherein patients display no response to existing hormone therapies. The standard of care often includes aggressive treatment options using chemotherapy, radiation therapy and various drugs to curb the growth of additional metastases. As such, there is a dire need for the development of innovative technologies for both its diagnosis and its management. Traditionally, scientific exploration of prostate cancer and its treatment options has been heavily reliant on animal models and two-dimensional (2D) in vitro technologies. However, both laboratory tools often fail to recapitulate the dynamic tumor microenvironment, which can lead to discrepancies in drug efficacy and side effects in a clinical setting. In light of the limitations of traditional animal models and 2D in vitro technologies, the emergence of microfluidics as a tool for prostate cancer research shows tremendous promise. Namely, microfluidics-based technologies have emerged as powerful tools for assessing prostate cancer cells, isolating circulating tumor cells, and examining their behaviour using tumor-on-a-chip models. As such, this review aims to highlight recent advancements in microfluidics-based technologies for the assessment of castration-resistant prostate cancer and its potential to advance current understanding and to improve therapeutic outcomes.
... Epithelial cell adhesion molecule (EpCAM), also known as TACSTD1 and classified as CD326 according to the leukocyte differentiation antigen, was initially discovered in colon cancer [1]; it is a type I transmembrane glycoprotein expressed by epithelial cells. And EpCAM is the first tumor-associated antigen identified by mAb [2,3], which participates in regulating cell adhesion, proliferation, differentiation, migration, and signal transduction [4]. Pathologically, it has been demonstrated that EpCAM is significantly upregulated in a diverse range of human malignancies, including lung carcinoma [5], esophageal carcinoma [6], gastric carcinoma [7], breast carcinoma [8], ovarian carcinoma [9], prostate carcinoma [10], and hepatocellular carcinoma [11]. ...
A “turn-on” aptasensor for label-free and cell-free EpCAM detection was constructed by employing magnetic α-Fe2O3/Fe3O4@Au nanocomposites as a matrix for signal amplification and double-stranded complex (SH-DNA/Apt probes) immobilization through Au-S binding. α-Fe2O3/Fe3O4@Au could be efficiently assembled into uniform and stable self-assembly films via magnetic-induced self-assembly technique on a magnetic glassy carbon electrode (MGCE). The effectiveness of the platform for EpCAM detection was confirmed through differential pulse voltammetry (DPV). Under optimized conditions, the platform exhibited excellent specificity for EpCAM, and a strong linear correlation was observed between the current and the logarithm of EpCAM protein concentration in the range 1 pg/mL–1000 pg/mL (R² = 0.9964), with a limit of detection (LOD) of 0.27 pg/mL. Furthermore, the developed platform demonstrated good stability during a 14-day storage test, with fluctuations remaining below 93.33% of the initial current value. Promising results were obtained when detecting EpCAM in spiked serum samples, suggesting its potential as a point-of-care (POC) testing.
Graphical Abstract
... Before performing an in vitro assay, this bioinformatics technique facilitates selecting the best possible compounds. Numerous research groups have used bioinformatics to create various in silico compounds [4][5][6]. A bioinformatics approach and computational techniques, such as molecular dynamics (MD) simulations, are used first to analyze new drug candidates in silico. ...
Azurin is a natural protein produced by Pseudomonas aeruginosa that exhibits potential anti-tumor, anti-HIV, and anti-parasitic properties. The current study aimed to investigate the potential of azurin protein against breast cancer using both in silico and in vitro analyses. The amino acid sequence of Azurin was used to predict its secondary and tertiary structures, along with its physicochemical properties, using online software. The resulting structure was validated and confirmed using Ramachandran plots and ERRAT2. The mature azurin protein comprises 128 amino acids, and the top-ranked structure obtained from I-TASSER was shown to have a molecular weight of 14 kDa and a quality factor of 100% by ERRAT2, with 87.4% of residues in the favored region of the Ramachandran plot. Docking and simulation studies of azurin protein were conducted using HDOCK and Desmond servers, respectively. The resulting analysis revealed that Azurin docked against p53 and EphB2 receptors demonstrated maximum binding affinity, indicating its potential to cause apoptosis. The recombinant azurin gene was successfully cloned and expressed in a BL21 (DE3) strain using a pET20b expression vector under the control of the pelB ladder, followed by IPTG induction. The azurin protein was purified to high levels using affinity chromatography, yielding 70 mg/L. In vitro cytotoxicity assay was performed using MCF-7 cells, revealing the significant cytotoxicity of the azurin protein to be 105 µg/mL. These findings highlight the potential of azurin protein as an anticancer drug candidate.
... As a multifunctional transmembrane glycoprotein, EpCAM consists of a larger extracellular structural domain of 265 amino acids (EpEX/EX) (Yahyazadeh Mashhadi (Gires et al. 2020). EpCAM was reported associated with signal proliferation, immune evasion by intercellular oligomerization and protein hydrolysis (Armstrong and Eck 2003;Baeuerle and Gires 2007;Keller et al. 2019), and as a key enhancer for structural integrity, adhesion of epithelial tissues and interaction with the underlying stromal layer (Gorges et al. 2012). In recent years, EpCAM was recognized as a stem cell, especially cancer stem cell (CSC) marker, and it is overexpressed on CSC and circulating tumor cells (CTCs), and therefore its detection can be used to track and isolate CTCs (Han et al. 2020;Murakami et al. 2019;Terris et al. 2010;Spizzo et al. 2011). ...
Background
Gastric cancer (GC) remains a global challenge due to its high morbidity and mortality rates especially in Asia as well as poor response to treatment. As a member of the adhesion protein family and transmembrane glycoprotein, EpCAM expressed excessively in cancer cells including GC cells. The database assay showed that EpCAM is excessively expressed and easily mutated in cancers, especially in early stage of GC.
Methods
To explore the roles EpCAM plays in oncogenesis and progression of GC, the expression of EpCAM was deleted in GC cells with CRISPR/Cas9 method, and then the changes of cell proliferation, apoptosis, motility and motility associated microstructures in EpCAM-deleted GC cells (EpCAM-/-SGC7901) were detected to evaluate the rules EpCAM played.
Results
The results showed that EpCAM deletion caused cell proliferation, motility and the development of motility-relevant microstructures inhibited significantly, apoptotic trend and contact inhibition enhanced in EpCAM-deleted GC cells. The results of western blot suggested that EpCAM modulates the expression of epithelial/endothelial mesenchymal transition (EMT) correlated genes. All results as above indicated that EpCAM plays important roles to enhance the oncogenesis, malignancy and progression as a GC enhancer.
Conclusions
Combining our results and published data together, the interaction of EpCAM with other proteins was also discussed and concluded in the discussion. Our results support that EpCAM can be considered as a novel target for the diagnosis and therapy of GC in future.
... Hence, CADM2 both induces EMT and supports migration of lung cancer cells to the central nervous system. Cells undergoing EMT also upregulate N-cadherins but downregulate expression of E-cadherins and the epithelial cell adhesion molecule (EpCAM) [24]. One of the regulators of E-cadherin is SNORA17B. ...
Cancer metastases into the brain constitute one of the most severe, but not uncommon, manifestations of cancer progression. Several factors control how cancer cells interact with the brain to establish metastasis. These factors include mediators of signaling pathways participating in migration, infiltration of the blood–brain barrier, interaction with host cells (e.g., neurons, astrocytes), and the immune system. Development of novel therapies offers a glimpse of hope for increasing the diminutive life expectancy currently forecasted for patients suffering from brain metastasis. However, applying these treatment strategies has not been sufficiently effective. Therefore, there is a need for a better understanding of the metastasis process to uncover novel therapeutic targets. In this review, we follow the journey of various cancer cells from their primary location through the diverse processes that they undergo to colonize the brain. These processes include EMT, intravasation, extravasation, and infiltration of the blood–brain barrier, ending up with colonization and angiogenesis. In each phase, we focus on the pathways engaging molecules that potentially could be drug target candidates.
... EpcAM was the first identified human tumor-associated antigen, and plays a critical role in tumor development (11). Therefore, EpcAM has been considered as a target of mAb therapies, including Adecatumumab (12) and Edrecolomab (13,14) in EpcAM-overexpressing breast, prostate, gastrointestinal and colorectal cancers. A humanized single chain Fv against EpcAM, fused to Pseudomonas exotoxin A, Oportuzumab monatox, has been evaluated in bladder cancer, as have been previously reviewed (15). ...
Epithelial cell adhesion molecule (EpCAM) is a type I transmembrane glycoprotein, which is highly expressed on tumor cells. As EpCAM plays a crucial role in cell adhesion, survival, proliferation, stemness, and tumorigenesis, it has been considered as a promising target for tumor diagnosis and therapy. Anti‑EpCAM monoclonal antibodies (mAbs) have been developed and have previously demonstrated promising outcomes in several clinical trials. An anti‑EpCAM mAb, EpMab‑37 (mouse IgG1, kappa) was previously developed by the authors, using the cell‑based immunization and screening method. In the present study, a defucosylated version of anti‑EpCAM mAb (EpMab‑37‑mG2a‑f) was generated to evaluate the antitumor activity against EpCAM‑positive cells. EpMab‑37‑mG2a‑f recognized EpCAM‑overexpressing CHO‑K1 (CHO/EpCAM) cells with a moderate binding‑affinity [dissociation constant (KD)=2.2x10‑8 M] using flow cytometry. EpMab‑37‑mG2a‑f exhibited potent antibody‑dependent cellular cytotoxicity (ADCC) and complement‑dependent cytotoxicity (CDC) for CHO/EpCAM cells by murine splenocytes and complements, respectively. Furthermore, the administration of EpMab‑37‑mG2a‑f significantly suppressed CHO/EpCAM xenograft tumor development compared with the control mouse IgG. EpMab‑37‑mG2a‑f also exhibited a moderate binding‑affinity (KD=1.5x10‑8 M) and high ADCC and CDC activities for a colorectal cancer cell line (Caco‑2 cells). The administration of EpMab‑37‑mG2a‑f to Caco‑2 tumor‑bearing mice significantly suppressed tumor development compared with the control. By contrast, EpMab‑37‑mG2a‑f never suppressed the xenograft tumor growth of Caco‑2 cells in which EpCAM was knocked out. On the whole, these results indicate that EpMab‑37‑mG2a‑f may exert antitumor activities against EpCAM‑positive cancers and may thus be a promising therapeutic regimen for colorectal cancer.
... The detailed site-specific N-glycosylation of HCT116-specific group and DKO1-specific group can be retrieved from Supplemental Data 5. Here, the sitespecific N-glycosylation of P16422|EPCAM is shown as an interesting example (Fig. 3b). EPCAM, aka CD326, is an oncogenic signaling molecule, a novel therapeutic target and cancer stem cell marker 20,21 . Glycosylation at N198 is instrumental to the stability of EPCAM 22 . ...
N-glycosylation is implicated in cancers and aberrant N-glycosylation is recognized as a hallmark of cancer. Here, we mapped and compared the site-specific N-glycoproteomes of colon cancer HCT116 cells and isogenic non-tumorigenic DNMT1/3b double knockout (DKO1) cells using Fbs1-GYR N-glycopeptide enrichment technology and trapped ion mobility spectrometry. Many significant changes in site-specific N-glycosylation were revealed, providing a molecular basis for further elucidation of the role of N-glycosylation in protein function. HCT116 cells display hypersialylation especially in cell surface membrane proteins. Both HCT116 and DKO1 show an abundance of paucimannose and 80% of paucimannose-rich proteins are annotated to reside in exosomes. The most striking N-glycosylation alteration was the degree of mannose-6-phosphate (M6P) modification. N-glycoproteomic analyses revealed that HCT116 displays hyper-M6P modification, which was orthogonally validated by M6P immunodetection. Significant observed differences in N-glycosylation patterns of the major M6P receptor, CI-MPR in HCT116 and DKO1 may contribute to the hyper-M6P phenotype of HCT116 cells. This comparative site-specific N-glycoproteome analysis provides a pool of potential N-glycosylation-related cancer biomarkers, but also gives insights into the M6P pathway in cancer. Comparative site-specific N-glycoproteome analysis of tumorigenic and non-tumorigenic colon cancer cells provides a pool of potential N-glycosylation related cancer biomarkers and insights into the mannose-6-phosphate pathway in cancer.
