Metabolic syndrome perturbs deglucosylation and reglucosylation in the glycoprotein folding cycle

Kuribara, Taiki; Imagawa, Ayami; Hirano, Masao; Ito, Yukishige; Totani, Kiichiro

doi:10.1002/1873-3468.13780

Cited by 8 publications

(3 citation statements)

References 41 publications

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“…To further clarify the effect of glycogen metabolism on the immune microenvironment, we compared the changes in the TME-related signatures between GEO-control and GEO-KO samples. As a resident enzyme of the endoplasmic reticulum, glucosidase II plays an important role in glucose metabolism and glycoprotein quality control ( Kuribara et al, 2020 ). As shown in Supplementary Figure S3A,B , the GMS of the GEO-KO samples were significantly lower than those of GEO-control samples ( t -test, p = 0.041, Supplementary Figure S3A,B ).…”

Section: Resultsmentioning

confidence: 99%

Glycogen Metabolism Predicts the Efficacy of Immunotherapy for Urothelial Carcinoma

Zhang

Zhou

et al. 2021

Front. Pharmacol.

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Urothelial cancer (UC) is one of the common refractory tumors and chemotherapy is the primary treatment for it. The advent of immune checkpoint inhibitors (ICI) has facilitated the development of treatment strategies for UC patients. To screen out UC patients sensitive to ICI, researchers have proposed that PD-L1, tumor mutation burden and TCGA molecular subtypes can be used as predictors of ICI efficacy. However, the performance of these predictors needs further validation. We need to identify novel biomarkers to screen out UC patients sensitive to ICI. In our study, we collected the data of two clinical cohorts: the ICI cohort and the TCGA cohort. The result of the multivariate Cox regression analysis showed that glycogen metabolism score (GMS) (HR = 1.26, p = 0.017) was the negative predictor of prognosis for UC patients receiving ICI treatment. Low-GMS patients had a higher proportion of patients achieving complete response or partial response to ICI. After the comparison of gene mutation status between high-GMS and low-GMS patients, we identified six genes with significant differences in mutation frequencies, which may provide new directions for potential drug targets. Moreover, we analyzed the immune infiltration status and immune-related genes expression between high-GMS and low-GMS patients. A reduced proportion of tumor-associated fibroblasts and elevated proportion of CD8+ T cells can be observed in low-GMS patients while several immunosuppressive molecules were elevated in the high-GMS patients. Using the sequencing data of the GSE164042 dataset, we also found that myeloid-derived suppressor cell and neutrophil related signature scores were lower in α-glucosidase knockout bladder carcinoma cells when compared to the control group. In addition, angiogenesis, classic carcinogenic pathways, immunosuppressive cells related pathways and immunosuppressive cytokine secretion were mainly enriched in high-GMS patients and cell samples from the control group. Finally, we suspected that the combination treatment of ICI and histone deacetylase inhibitors may achieve better clinical responses in UC patients based on the analysis of drug sensitivity data. In conclusion, our study revealed the predictive value of GMS for ICI efficacy of UC patients, providing a novel perspective for the exploration of new drug targets and potential treatment strategies.

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Section: Resultsmentioning

confidence: 99%

Glycogen Metabolism Predicts the Efficacy of Immunotherapy for Urothelial Carcinoma

Zhang

Zhou

et al. 2021

Front. Pharmacol.

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“…Recently, we have reported perturbation of CNX/CRT cycle in obesity and obese type 2 diabetes model rats, namely, Zucker fatty rat (ZF) and Zucker diabetic fatty rat (ZDF) [ 103 , 104 ] using the reconstruction approach. To summarize simply, all CNX/CRT cycle-related proteins’ expression and activity were reduced in ZF.…”

Section: Oligomannose-type Glycan Processing In Glycoprotein Erqc And...mentioning

confidence: 99%

Oligomannose-Type Glycan Processing in the Endoplasmic Reticulum and Its Importance in Misfolding Diseases

Kuribara

Totani

2022

Biology

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Glycoprotein folding plays a critical role in sorting glycoprotein secretion and degradation in the endoplasmic reticulum (ER). Furthermore, relationships between glycoprotein folding and several diseases, such as type 2 diabetes and various neurodegenerative disorders, are indicated. Patients’ cells with type 2 diabetes, and various neurodegenerative disorders induce ER stress, against which the cells utilize the unfolded protein response for protection. However, in some cases, chronic and/or massive ER stress causes critical damage to cells, leading to the onset of ER stress-related diseases, which are categorized into misfolding diseases. Accumulation of misfolded proteins may be a cause of ER stress, in this respect, perturbation of oligomannose-type glycan processing in the ER may occur. A great number of studies indicate the relationships between ER stress and misfolding diseases, while little evidence has been reported on the connection between oligomannose-type glycan processing and misfolding diseases. In this review, we summarize alteration of oligomannose-type glycan processing in several ER stress-related diseases, especially misfolding diseases and show the possibility of these alteration of oligomannose-type glycan processing as indicators of diseases.

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“…UGGT is inhibited by its product uridine diphosphate ( UDP) 9 and squaryl derivatives of UDP 10 ; by the non-hydrolyzable UDP-Glucose (UDP-Glc) cofactor analog UDP-2-deoxy-2-fluoro-D-glucose (U2F); and by synthetic analogs of the N -linked Man 9 GlcNAc 2 glycan substrate, 11 , 12 but obviously none of these molecules are UGGT specific. Selective and potent UGGT modulators would be important reagents for interrogating the cell biology of the secretory pathway, as well as having therapeutic potential in several areas of medical science (such as virology, 13 , 14 , 15 metabolic and rare genetic disease, 16 , 17 , 18 immunology, 5 and cancer 19 , 20 , 21 ), biotechnology, and agricultural science. 22 , 23 , 24 , 25 …”

Section: Introductionmentioning

confidence: 99%

A quinolin-8-ol sub-millimolar inhibitor of UGGT, the ER glycoprotein folding quality control checkpoint

Guay,

Ibba,

Kiappes

et al. 2023

iScience

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Metabolic syndrome perturbs deglucosylation and reglucosylation in the glycoprotein folding cycle

Cited by 8 publications

References 41 publications

Glycogen Metabolism Predicts the Efficacy of Immunotherapy for Urothelial Carcinoma

Glycogen Metabolism Predicts the Efficacy of Immunotherapy for Urothelial Carcinoma

Oligomannose-Type Glycan Processing in the Endoplasmic Reticulum and Its Importance in Misfolding Diseases

A quinolin-8-ol sub-millimolar inhibitor of UGGT, the ER glycoprotein folding quality control checkpoint

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