Altered glycosylation associated with dedifferentiation of hepatocellular carcinoma: a lectin microarray-based study

Takayama, Hiroomi; Ohta, Masayuki; Iwashita, Yukio; Uchida, Hajime; Yuki, Satoshi; Yada, Kazuhiro; Ito, Masafumi

doi:10.1186/s12885-020-6699-5

Cited by 32 publications

(23 citation statements)

References 45 publications

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“…These processes are mediated by cell‐surface glycoproteins, glycolipids, and glycopolymers, and glycans expressed in the glycocalyx are unique identifiers of cell type that can indicate disease and could serve as drug targets. For example, in gastric cancer, [2] liver cancer, [3] and breast cancer, [4] there is an overexpression of mannose and mannose receptors. While N ‐acetylgalactosoamine is overexpressed in colorectal cancer, [5] and β‐galactose and N ‐acetylglucosamine are prevalent on the surface of malignant melanoma cells [5–6] .…”

Section: Introductionmentioning

confidence: 99%

Regiochemical Effects on the Carbohydrate Binding and Selectivity of Flexible Synthetic Carbohydrate Receptors with Indole and Quinoline Heterocyclic Groups

et al. 2021

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Synthetic carbohydrate receptors (SCRs) that bind cell‐surface carbohydrates could be used for disease detection, drug‐delivery, and therapeutics, or for the site‐selective modification of complex carbohydrates, but their potential has not been realized because of remaining challenges associated with binding affinity and substrate selectivity. We have reported recently a series of flexible SCRs based upon a biaryl core with four pendant heterocyclic groups that bind glycans selectively through noncovalent interactions. Here we continue to explore the role of heterocycles on substrate selectivity by expanding our library to include a series of indole and quinoline heterocycles that vary in their regiochemistry of attachment to the biaryl core. The binding of these SCRs to a series of biologically‐relevant carbohydrates was studied by 1H NMR titrations in CD2Cl2 and density‐functional theory calculations. We find SCR030, SCR034 and SCR037 are selective, SCR031, SCR032, and SCR039 are strong binders, and SCR033, SCR035, SCR036, and SCR038 are promiscuous and bind weakly. Computational analysis reveals the importance of C−H⋅⋅⋅π and H‐bonding interactions in defining the binding properties of these new receptors. By combining these data with those obtained from our previous studies on this class of flexible SCRs, we develop a series of design rules that account for the binding of all SCRs of this class, and anticipate the binding of future, not‐yet imagined tetrapodal SCRs.

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Section: Introductionmentioning

confidence: 99%

Regiochemical Effects on the Carbohydrate Binding and Selectivity of Flexible Synthetic Carbohydrate Receptors with Indole and Quinoline Heterocyclic Groups

et al. 2021

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“…This signaling pathway plays a key role in controlling tumor progression. 40–42 From this perspective, MGAT1 functions in promoting the synthesis of triglycerides and the development of tumors. Our study indicated that MGAT1 has a strong positive correlation with T cells CD4 naive and monocytes but a strong negative correlation with neutrophils and T cells CD8.…”

Section: Discussionmentioning

confidence: 99%

Step-by-Step Construction of Gene Co-Expression Network Analysis for Identifying Novel Biomarkers of Sepsis Occurrence and Progression

Tong

et al. 2021

IJGM

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Background Sepsis is the leading cause of death in critically ill patients. Although it is well known that the immune system plays a key role in sepsis, exactly how it works remains unknown. Methods In our study, we used weighted gene co-expression network analysis (WGCNA) to screen out the immune-related genes that may play a critical role in the process of sepsis. Results A total of three sepsis-related hub genes were screened for further verification. Subsequent analysis of immune subtypes suggested their potential predictive effect in the clinic. Conclusion Our study shows that three immune-related genes CHMP1A, MED15 and MGAT1 are important biomarkers of sepsis. The screened genes may help to distinguish normal individuals from patients with different degrees of sepsis.

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“…The copyright holder for this preprint (which this version posted April 29, 2021. ; https://doi.org/10.1101/2021.04.28.441869 doi: bioRxiv preprint independent activation of X-box binding protein 1 (XBP1), misregulation of Nacetylglucosaminyltransferase, and downregulation of α-mannosidase I and mannosyl(α-1,3-)glycoprotein β-1,2-N-acetylglucosaminyltransferase (MGAT1). 11,12,51,52 Stress-independent activation of XBP1, for instance, was found to reduce sialylation and bisecting GlcNAc while increasing the levels of high-mannose glycans in HEK293 and HeLa cells by affecting mannosidase expression. 51 The significant reduction of α-mannosidase I expression found in cholangiocarcinoma cells was correlated to the elevation of high-mannose glycans and a more metastatic phenotype.…”

Section: Discussionmentioning

confidence: 99%

“…12 Takayama et al have shown that increased high-mannose glycan expression, detected in surgical specimens of hepatocellular carcinoma, was associated with decreased expression of MGAT1, a key glycosyltransferase that converts high-mannose glycans to complex-or hybrid-type N-glycans. 11 Meanwhile, high-mannose glycans at the helical domain of transferrin receptor protein 1 appear to trigger structural changes that improve noncovalent interaction energies, resulting in cell migration enhancement in metastatic cholangiocarcinoma. 12 A recent publication assessing the impact of high-mannose glycans on bone-marrow-derived mesenchymal stromal cells has provided evidence that these glycans alter the physical and structural properties of the cells themselves, decreasing their size and increasing motility, which may in part explain the greater metastatic potential seen in other cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…5 Analysis of large cohorts of paired breast cancerous and adjacent non-tumor tissues found a high-mannose glycan (Man8) along with a triantennary glycan to be dramatically increased in the membrane fraction of tumors. 6 Increased abundance of high-mannose glycans has also been observed in colorectal tumor tissues [7][8][9] , hepatocellular carcinoma 10,11 , metastatic cholangiocarcinoma 12 , lung adenocarcinoma 13 , pancreatic cancer 14 , ovarian cancer 15,16 , prostate cancer 17 and skin basal cell carcinoma and squamous cell carcinoma 18 . Collectively, the aberrant increase of high-mannose glycans on malignant cells may provide a unique biomarker for drug development.…”

Section: Introductionmentioning

confidence: 99%

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Antitumor activity of a lectibody targeting cancer-associated high-mannose glycans

Dent

et al. 2021

Preprint

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Aberrant protein glycosylation is a hallmark of cancer, but few drugs targeting cancer glycobiomarkers are currently available. Here, we show that a ″lectibody″ consisting of the high-mannose glycan-binding lectin Avaren and human IgG1 Fc (AvFc) selectively recognizes a range of cell lines derived from lung, breast, colon and blood cancers at nanomolar concentrations. AvFc's binding to the non-small cell lung cancer (NSCLC) cell lines A549 and H460 was characterized in detail. Co-immunoprecipitation proteomics analysis revealed that epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R) are among the lectibody's common targets in these cells. AvFc blocked the activation of EGFR and IGF1R by their respective ligands in A549 cells and inhibited the migration of A549 and H460 cells upon stimulation with EGF and IGF1. Furthermore, AvFc induced potent Fc-mediated cytotoxic effects and significantly retarded A549 and H460 tumor growth in SCID mice. Immunohistochemistry analysis of primary lung tissues from NSCLC patients demonstrated that AvFc preferentially binds to tumors over adjacent non-tumor tissues. Our findings provide evidence that increased abundance of high-mannose glycans in the glycocalyx of cancer cells can be a druggable target, and AvFc may provide a new tool to probe and target this tumor-associated glycobiomarker.

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Altered glycosylation associated with dedifferentiation of hepatocellular carcinoma: a lectin microarray-based study

Cited by 32 publications

References 45 publications

Regiochemical Effects on the Carbohydrate Binding and Selectivity of Flexible Synthetic Carbohydrate Receptors with Indole and Quinoline Heterocyclic Groups

Regiochemical Effects on the Carbohydrate Binding and Selectivity of Flexible Synthetic Carbohydrate Receptors with Indole and Quinoline Heterocyclic Groups

Step-by-Step Construction of Gene Co-Expression Network Analysis for Identifying Novel Biomarkers of Sepsis Occurrence and Progression

Antitumor activity of a lectibody targeting cancer-associated high-mannose glycans

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