International Journal of Molecular Sciences

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Dr. Takeshi Sato

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Laboratory of Glycobiology, Department of Bioengineering, Nagaoka University of Technology, Nagaoka, Niigata 940-2188, Japan
Interests: transcriptional mechanism; glycosylation; glycosyltransferase; glycan function; glycan remodeling; cancer- and disease-related glycan

Special Issue Information

Dear Colleagues,

Glycosylation is an important modification of functional molecules, for instance, cell adhesion molecules and growth factor receptors. Upon malignant transformation and diseases, drastic changes in the glycan structures occur, and functional molecules modified with such glycans exhibit abnormality and dysfunction in cancer and diseases. The changes of glycosylation are brought about by the altered gene expression of glycosyltransferases in glycan biosynthesis. However, the transcriptional mechanism of glycosyltransferases remains largely unknown concerning the relation to cancer and diseases. The understanding of the mechanism will shed light on the regulatory mechanism of glycosylation in cancer and diseases with a fresh angle and contribute to the development of novel drug screening and therapeutic strategies. This Special Issue calls for the submission of original research articles and reviews, including recent progress and knowledge on “Transcriptional Mechanism of Glycosyltransferase Genes Related to Cancer and Diseases”.

Dr. Takeshi Sato
Guest Editor

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Keywords

transcriptional regulation
transcription factor
promoter
gene expression
glycoprotein
glycolipid
glycosylation
glycan biosynthesis

Published Papers (2 papers)

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Research

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14 pages, 3357 KiB

Open AccessArticle

Glycosyltransferase B4GALNT2 as a Predictor of Good Prognosis in Colon Cancer: Lessons from Databases

by Michela Pucci, Nadia Malagolini and Fabio Dall’Olio

Int. J. Mol. Sci. 2021, 22(9), 4331; https://doi.org/10.3390/ijms22094331 - 21 Apr 2021

Cited by 13 | Viewed by 2531

Abstract

Background: glycosyltransferase B4GALNT2 and its cognate carbohydrate antigen Sd^a are highly expressed in normal colon but strongly downregulated in colorectal carcinoma (CRC). We previously showed that CRC patients expressing higher B4GALNT2 mRNA levels displayed longer survival. Forced B4GALNT2 expression reduced the malignancy and stemness of colon cancer cells. Methods: Kaplan–Meier survival curves were determined in “The Cancer Genome Atlas” (TCGA) COAD cohort for several glycosyltransferases, oncogenes, and tumor suppressor genes. Whole expression data of coding genes as well as miRNA and methylation data for B4GALNT2 were downloaded from TCGA. Results: the prognostic potential of B4GALNT2 was the best among the glycosyltransferases tested and better than that of many oncogenes and tumor suppressor genes; high B4GALNT2 expression was associated with a lower malignancy gene expression profile; differential methylation of an intronic B4GALNT2 gene position and miR-204-5p expression play major roles in B4GALNT2 regulation. Conclusions: high B4GALNT2 expression is a strong predictor of good prognosis in CRC as a part of a wider molecular signature that includes ZG16, ITLN1, BEST2, and GUCA2B. Differential DNA methylation and miRNA expression contribute to regulating B4GALNT2 expression during colorectal carcinogenesis. Full article

(This article belongs to the Special Issue Transcriptional Mechanism of Glycosyltransferase Genes Related to Cancer and Diseases)

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Review

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20 pages, 1010 KiB

Open AccessReview

The Role of Glycosyltransferases in Colorectal Cancer

by Cecilia Fernández-Ponce, Noelia Geribaldi-Doldán, Ismael Sánchez-Gomar, Roberto Navarro Quiroz, Linda Atencio Ibarra, Lorena Gomez Escorcia, Ricardo Fernández-Cisnal, Gustavo Aroca Martinez, Francisco García-Cózar and Elkin Navarro Quiroz

Int. J. Mol. Sci. 2021, 22(11), 5822; https://doi.org/10.3390/ijms22115822 - 30 May 2021

Cited by 21 | Viewed by 6926

Abstract

Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Post-translational modifications (PTMs) have been extensively studied in malignancies due to its relevance in tumor pathogenesis and therapy. This review is focused on the dysregulation of glycosyltransferase expression in CRC and its impact in cell function and in several biological pathways associated with CRC pathogenesis, prognosis and therapeutic approaches. Glycan structures act as interface molecules between cells and their environment and in several cases facilitate molecule function. CRC tissue shows alterations in glycan structures decorating molecules, such as annexin-1, mucins, heat shock protein 90 (Hsp90), β1 integrin, carcinoembryonic antigen (CEA), epidermal growth factor receptor (EGFR), insulin-like growth factor-binding protein 3 (IGFBP3), transforming growth factor beta (TGF-β) receptors, Fas (CD95), PD-L1, decorin, sorbin and SH3 domain-containing protein 1 (SORBS1), CD147 and glycosphingolipids. All of these are described as key molecules in oncogenesis and metastasis. Therefore, glycosylation in CRC can affect cell migration, cell–cell adhesion, actin polymerization, mitosis, cell membrane repair, apoptosis, cell differentiation, stemness regulation, intestinal mucosal barrier integrity, immune system regulation, T cell polarization and gut microbiota composition; all such functions are associated with the prognosis and evolution of the disease. According to these findings, multiple strategies have been evaluated to alter oligosaccharide processing and to modify glycoconjugate structures in order to control CRC progression and prevent metastasis. Additionally, immunotherapy approaches have contemplated the use of neo-antigens, generated by altered glycosylation, as targets for tumor-specific T cells or engineered CAR (Chimeric antigen receptors) T cells. Full article

(This article belongs to the Special Issue Transcriptional Mechanism of Glycosyltransferase Genes Related to Cancer and Diseases)

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