Fucosylation in cancer biology and its clinical applications

Shan, Ming; Yang, Dandan; Dou, Huaiqian; Zhang, Lijuan

doi:10.1016/bs.pmbts.2019.01.002

Cited by 83 publications

(55 citation statements)

References 135 publications

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“…Increasing numbers of studies have identified important and specific roles for fucosylated glycoconjugates in tumorigenesis and how they correlate with the established hallmarks of cancer [10]. Deregulation of fucosylation has been reported in several cancer types, and the resulting divergent functional consequences are likely attributed to the presence/absence of specific structural types of fucosylation branching that can differentially influence protein function [11,12]. Increased fucosylation has been attributed to metastatic properties such as, for example, enhancing adhesion of metastatic cancer cells to endothelia cells [1,4,13].…”

Section: Introductionmentioning

confidence: 99%

The Diverse Contributions of Fucose Linkages in Cancer

Keeley

Yang

Lau

2019

Cancers

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Fucosylation is a post-translational modification of glycans, proteins, and lipids that is responsible for many biological processes. Fucose conjugation via α(1,2), α(1,3), α(1,4), α(1,6), and O’- linkages to glycans, and variations in fucosylation linkages, has important implications for cancer biology. This review focuses on the roles that fucosylation plays in cancer, specifically through modulation of cell surface proteins and signaling pathways. How L-fucose and serum fucosylation patterns might be used for future clinical diagnostic, prognostic, and therapeutic approaches will be discussed.

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Section: Introductionmentioning

confidence: 99%

The Diverse Contributions of Fucose Linkages in Cancer

Keeley

Yang

Lau

2019

Cancers

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“…Currently, the study of fucosylation in cancer is mainly focused on the abnormality of fucosyltransferase. The differential expression of the fucosyltransferase has been observed in breast, lung, liver, brain, and thyroid cancer 20 . However, fucose synthesis abnormality in cancers has seldom been reported.…”

Section: Introductionmentioning

confidence: 99%

TSTA3 facilitates esophageal squamous cell carcinoma progression through regulating fucosylation of LAMP2 and ERBB2

et al. 2020

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Background: TSTA3 gene encodes an enzyme responsible for synthesis of GDP-L-fucose as the only donor in fucosylation. This study was designed to explore clinical value, function and underlying mechanism of TSTA3 in the development of esophageal squamous cell carcinoma (ESCC). Methods: Whole genomic sequencing data from 663 ESCC patients and RNA sequencing data from 155 ESCC patients were used to analyze the copy number variation and mRNA expression of TSTA3 respectively. Immunohistochemistry based or not based on the tissue microarrays was used to detect its protein expression. Transwell assay and in vivo metastasis assay were used to study the effect of TSTA3 on invasion and metastasis of ESCC. Immunofluorescence was used to analyze fucosylation level. N-glycoproteomics and proteomics analysis, Lens Culinaris Agglutinin (LCA) and Ulex Europaeus Agglutinin I (UEA-I) affinity chromatography, immunoprecipitation, glycosyltransferase activity kit and rescue assay were used to explore the mechanism of TSTA3. Results: TSTA3 was frequently amplified and overexpressed in ESCC. TSTA3 amplification and protein overexpression were significantly associated with malignant progression and poor prognosis of ESCC patients. TSTA3 knockdown significantly suppressed ESCC cells invasion and tumor dissemination by decreasing fucosylation level. Conversely, exogenous overexpression of TSTA3 led to increased invasion and tumor metastasis in vitro and in vivo by increasing fucosylation level. Moreover, core fucosylated LAMP2 and terminal fucosylated ERBB2 might be mediators of TSTA3-induced pro-invasion in ESCC and had a synergistic effect on the process. Peracetylated 2-F-Fuc, a fucosyltransferase activity inhibitor, reduced TSTA3 expression and fucosylation modification of LAMP2 and ERBB2, thereby inhibiting ESCC cell invasion. Conclusion: Our results indicate that TSTA3 may be a driver of ESCC metastasis through regulating fucosylation of LAMP2 and ERBB2. Fucosylation inhibitor may have prospect to suppress ESCC metastasis by blocking aberrant fucosylation.

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“…Fucosylation contributes to various biochemical events involving pathogen–host interactions, leukocyte extravasation, and signaling. Aberrant fucosylation is a major signature of malignant transformation as fucosylation has been found to be involved in cell proliferation, invasion, and metastasis [ 14 ]. Kumar et al reported that serum fucose levels are significantly increased in patients with oral cancer, correlating with the histopathological grading [ 30 ].…”

Section: Resultsmentioning

confidence: 99%

“…Generally, the main glycosylation alterations in cancer are the increased fucosylation and higher degree of branching due to altered fucose metabolism and N-acetyl-glucosamine-transferase activity [ 13 ]. Fucose residues can normally occur on a wide range of molecules as most IgG glycans are α1-6 fucosylated, while ABO blood group antigens are fucosylated glycans as well [ 14 ]. Alterations in GDP-fucose synthesis, fucosyl-transferase, and fucosidase activity can lead to aberrant fucosylation, which has been identified as a major signature of uncontrolled cell proliferation, tumor cell invasion, and metastasis [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Fucose residues can normally occur on a wide range of molecules as most IgG glycans are α1-6 fucosylated, while ABO blood group antigens are fucosylated glycans as well [ 14 ]. Alterations in GDP-fucose synthesis, fucosyl-transferase, and fucosidase activity can lead to aberrant fucosylation, which has been identified as a major signature of uncontrolled cell proliferation, tumor cell invasion, and metastasis [ 14 ]. Increased branching of glycans—a shift from bi-antennary to tri- and tetra-antennary structures—is also found to be correlated with cellular transformation and progression [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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The Analysis of Human Serum N-Glycosylation in Patients with Primary and Metastatic Brain Tumors

Váradi

Hajdu

Farkas

et al. 2021

Life

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The identification of patients with different brain tumors is solely built on imaging diagnostics, indicating the need for novel methods to facilitate disease recognition. Glycosylation is a chemical modification of proteins, reportedly altered in several inflammatory and malignant diseases, providing a potential alternative route for disease detection. In this paper, we report the quantitative analysis of serum N-glycosylation of patients diagnosed with primary and metastatic brain tumors. PNGase-F-digested and procainamide-labeled serum glycans were purified by magnetic nanoparticles, followed by quantitative liquid chromatographic analysis. The glycan structures were identified by the combination of single quad mass spectrometric detection and exoglycosidase digestions. Linear discriminant analysis provided a clear separation of different disease groups and healthy controls based on their N-glycome pattern. Altered distribution of biantennary neutral, sialylated but nonfucosylated, and sialylated–fucosylated structures were found to be the most significant changes. Our results demonstrate that serum glycosylation monitoring could improve the detection of malignancy.

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Fucosylation in cancer biology and its clinical applications

Cited by 83 publications

References 135 publications

The Diverse Contributions of Fucose Linkages in Cancer

The Diverse Contributions of Fucose Linkages in Cancer

TSTA3 facilitates esophageal squamous cell carcinoma progression through regulating fucosylation of LAMP2 and ERBB2

The Analysis of Human Serum N-Glycosylation in Patients with Primary and Metastatic Brain Tumors

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