α1,6-Fucosyltransferase contributes to cell migration and proliferation as well as to cancer stemness features in pancreatic carcinoma

Liang, Caixia; Fukuda, Tomohiko; Isaji, Tomoya; Duan, Chengwei; Song, Wanli; Gu, Jianguo

doi:10.1016/j.bbagen.2021.129870

Cited by 19 publications

(13 citation statements)

References 60 publications

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“…However, altered fucosylated structures frequently appear during a variety of pathological processes, such as inflammatory response, tumorigenesis and metastasis ( Li, Hsu, Mountz, and Allen, 2018 ). For instance, deficiency of core fucosylation (α1,6-fucose) that catalyzed by α1,6-fucosyltransferase (FUT8), reduced the pancreatic cancer cell proliferation and migration ( Liang et al, 2021 ). In addition, accumulating studies have shown that dysregulation of fucosyltransferase 2 (FUT2) was associated with various human disorders, such as infection and chronic inflammatory diseases ( Goto, Uematsu, and Kiyono, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of fucosylation by 2-fluorofucose attenuated acetaminophen-induced liver injury via its anti-inflammation and anti-oxidative stress effects

Liu

Shi

et al. 2022

Front. Pharmacol.

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Fucosylation is a common glycan terminal modification, which has been reported to be inhibited by 2-fluorofucose (2FF) both in vivo and in vitro. The present study aimed to investigate the effect of 2FF on acetaminophen (APAP)-induced acute liver injury, and further clarified the possible mechanisms. In the present study, inhibition of fucosylation by 2FF relieved APAP-induced acute liver injury in vivo. Pretreatment with 2FF remarkably suppressed APAP-induced oxidative stress and mitochondria damage. 2FF markedly enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and simultaneously promoted the expression of downstream proteins including HO-1 and NQO1. Furthermore, pretreatment with 2FF significantly suppressed the expression of inflammation-associated proteins, such as COX2 and iNOS. The data from lectin blot assay revealed that the alteration of α1,6-fucosylation was involved in APAP-induced acute liver injury. The second part of this study further confirmed that the enhancements to antioxidant capacity of 2FF pretreatment and α1,6-fucose deficiency were related to Nrf2/keap1 and NF-κB signaling pathways in HepG2 cells. Taken together, the current study suggested that 2FF might have a potential therapeutic effect for APAP-induced acute liver injury.

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Section: Introductionmentioning

confidence: 99%

Inhibition of fucosylation by 2-fluorofucose attenuated acetaminophen-induced liver injury via its anti-inflammation and anti-oxidative stress effects

Liu

Shi

et al. 2022

Front. Pharmacol.

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“…Additionally, C1GALT1 also modifies O-glycans on α integrins, especially the αV and α5 subunits, and promotes PC cell invasiveness through the integrin–FAK signaling [ 225 ]. It is worth mentioning that deficiency of α1,6-Fucosyltransferase (FUT8), a sole enzyme responsible for catalyzing core fucosylation, inhibited cell migration and proliferation in both MIA PaCa-2 and PANC-1 cells, which may arise through the fucosylation on β1 integrin [ 226 ], suggesting FUT8 may be a potential therapeutic target for PDAC. Further studies are needed to focus on the role N -glycosylation of integrin β1 and its related glycosyltransferases during PC progression.…”

Section: Future Expectationsmentioning

confidence: 99%

Integrin β1 in Pancreatic Cancer: Expressions, Functions, and Clinical Implications

Peng

Chen

et al. 2022

Cancers

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Pancreatic cancer (PC) is characterized by rapid progression and a high mortality rate. The current treatment is still based on surgical treatment, supplemented by radiotherapy and chemotherapy, and new methods of combining immune and molecular biological treatments are being explored. Despite this, the survival rate of PC patients is still very disappointing. Therefore, clarifying the molecular mechanism of PC pathogenesis and developing precisely targeted drugs are key to improving PC prognosis. As the most common β subunit of the integrin family, integrin β1 has been proved to be closely related to the vascular invasion, distant metastasis, and survival of PC patients, and treatment targeting integrin β1 in PC has gained initial success in animal models. In this review, we summarize the various signaling pathways by which integrins are involved in PC, focusing on the roles of integrin β1 in the malignant behaviors of PC. Additionally, recent studies regarding the feasibility of integrin β1 as a diagnostic and prognostic biomarker in PC are also discussed. Finally, we present the progress of several integrin β1-based clinical trials to highlight the potential of integrin β1 as a target for personalized therapy in PC.

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“…For example, upregulation or downregulation of FUT8 encoding an α1,6-fucosyltransferase can predict an increase or decrease in the fucosylation of the innermost N-acetylglucosamine (GlcNAc) of N-linked glycans, called core fucose. Its expression is partly associated with cancer progression and can thus act as a tumor marker [13][14][15]. It is also involved in regulating antibody-dependent cellular cytotoxicity (ADCC) [15], but it has not been shown to be associated with oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Fucosyltransferase 8 (FUT8) and core fucose expression in oxidative stress response

Kyunai

Sakamoto²,

Koreishi³

et al. 2023

PLoS ONE

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GlycoMaple is a new tool to predict glycan structures based on the expression levels of 950 genes encoding glycan biosynthesis-related enzymes and proteins using RNA-seq data. The antioxidant response, protecting cells from oxidative stress, has been focused on because its activation may relieve pathological conditions, such as neurodegenerative diseases. Genes involved in the antioxidant response are defined within the GO:0006979 category, including 441 human genes. Fifteen genes overlap between the glycan biosynthesis-related genes defined by GlycoMaple and the antioxidant response genes defined by GO:0006979, one of which is FUT8. 5-Hydroxy-4-phenyl-butenolide (5H4PB) extracted from Chinese aromatic vinegar induces the expression of a series of antioxidant response genes that protect cells from oxidative stress via activation of the nuclear factor erythroid 2-related factor 2–antioxidant response element pathway. Here, we show that FUT8 is upregulated in both our RNA-seq data set of 5H4PB-treated cells and publicly available RNA-seq data set of cells treated with another antioxidant, sulforaphane. Applying our RNA-seq data set to GlycoMaple led to a prediction of an increase in the core fucose of N-glycan that was confirmed by flow cytometry using a fucose-binding lectin. These results suggest that FUT8 and core fucose expression may increase upon the antioxidant response.

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α1,6-Fucosyltransferase contributes to cell migration and proliferation as well as to cancer stemness features in pancreatic carcinoma

Cited by 19 publications

References 60 publications

Inhibition of fucosylation by 2-fluorofucose attenuated acetaminophen-induced liver injury via its anti-inflammation and anti-oxidative stress effects

Inhibition of fucosylation by 2-fluorofucose attenuated acetaminophen-induced liver injury via its anti-inflammation and anti-oxidative stress effects

Integrin β1 in Pancreatic Cancer: Expressions, Functions, and Clinical Implications

Fucosyltransferase 8 (FUT8) and core fucose expression in oxidative stress response

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