A5010280265- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Cell Adhesion Molecules Research
- Monoclonal and Polyclonal Antibodies Research
- Carbohydrate Chemistry and Synthesis
- Ovarian cancer diagnosis and treatment
- Cancer Cells and Metastasis
- TGF-β signaling in diseases
- Immune Cell Function and Interaction
- Ubiquitin and proteasome pathways
- Cancer Mechanisms and Therapy
- Endometrial and Cervical Cancer Treatments
- NF-κB Signaling Pathways
- Helicobacter pylori-related gastroenterology studies
- Cellular Mechanics and Interactions
- PI3K/AKT/mTOR signaling in cancer
- Cell death mechanisms and regulation
- Immunotherapy and Immune Responses
- Autophagy in Disease and Therapy
- Proteoglycans and glycosaminoglycans research
- Cancer-related Molecular Pathways
- Endometriosis Research and Treatment
- Protein Degradation and Inhibitors
- RNA Research and Splicing
- PARP inhibition in cancer therapy
Tohoku Medical and Pharmaceutical University
2016-2025
Komatsu (Japan)
2014-2025
The University of Tokyo
1996-2025
Nagasaki University
2025
JR Tokyo General Hospital
2022
University of Tokyo Hospital
2022
Science for Life Laboratory
2020-2021
Uppsala University
2020-2021
Centre for Innovation in Regulatory Science
2011-2015
Aichi Medical University
2008-2012
Fibronectin (FN) has a complex pattern of alternative splicing at the mRNA level. One alternatively spliced segments, EDA, is prominently expressed during biological processes involving substantial cell migration and proliferation, such as embryonic development, malignant transformation, wound healing. To examine function EDA segment, we overexpressed recombinant FN isoforms with or without in CHO cells compared their cell-adhesive activities using purified proteins. EDA+ was significantly...
Extracellular matrix (ECM), which provides critical scaffolds for all adhesive cells, regulates proliferation, differentiation, and apoptosis. Different cell types employ customized ECMs, are thought to play important roles in the generation of so-called niches that contribute cell-specific functions. The molecular entities these however, have not been elucidated. Here, we describe a strategy transcriptome-wide identification ECM proteins based on computational screening >60,000 full-length...
N-Glycosylation of integrin alpha5beta1 plays a crucial role in cell spreading, migration, ligand binding, and dimer formation, but the detailed mechanisms by which N-glycosylation mediates these functions remain unclear. In previous study, we showed that three potential sites (alpha5S3-5) on beta-propeller alpha5 subunit are essential to functional expression subunit. particular, site 5 (alpha5S5) is most important for its surface. this function N-glycans beta1 was investigated using...
Up-regulation of core fucosylation catalyzed by α1,6-fucosyltransferase (Fut8) has been observed in hepatocellular carcinoma (HCC). Here, to explore the role Fut8 expression hepatocarcinogensis, we established chemical-induced HCC models male wild-type (WT; Fut8+/+), hetero (Fut8+/-), and knockout (KO; mice use diethylnitrosamine (DEN) pentobarbital (PB). In Fut8+/+ Fut8+/- mice, multiple large vascularized nodules were induced with an increased after DEN PB treatment. However, formation...
The epithelial-to-mesenchymal transition (EMT) plays crucial roles in embryonic development, wound healing, tissue repair, and cancer progression. Results of this study show how transforming growth factor β1 (TGF-β1) down-regulates expression N-acetylglucosaminyltransferase III (GnT-III) during EMT-like changes. Treatment with TGF-β1 resulted a decrease E-cadherin GnT-III expression, as well its product, the bisected N-glycans, which was confirmed by erythro-agglutinating phytohemagglutinin...
Core fucosylation is one of the most important glycosylation events in progression liver cancer. For this study, we used an easily handled L-fucose analog, 2-fluoro-L-fucose (2FF), which interferes with normal synthesis GDP-fucose, and verified its potential roles regulating core cell behavior HepG2 cancer line. Results obtained from lectin blot flow cytometry analysis clearly showed that 2FF treatment dramatically inhibited fucosylation, was also confirmed via mass spectrometry analysis....
Previously, we reported that α1,6-fucosyltransferase (Fut8)-deficient (Fut8−/−) mice exhibit emphysema-like changes in the lung and severe growth retardation due to dysregulation of TGF-β1 EGF receptors abnormal integrin activation, respectively. To study role α1,6-fucosylation brain tissue where Fut8 is highly expressed, examined Fut8−/− using a combination neurological behavioral tests. exhibited multiple abnormalities consistent with schizophrenia-like phenotype. displayed increased...
Ag recognition and Ab production in B cells are major components of the humoral immune response. In current study, we found that core fucosylation catalyzed by α1,6-fucosyltransferase (Fut8) was required for BCR subsequent signal transduction. Moreover, compared with 3-83 cells, coalescing lipid rafts Ag-BCR endocytosis were substantially reduced Fut8-knockdown (3-83-KD) p31 stimulation then completely restored reintroduction Fut8 gene to 3-83-KD cells. Indeed, Fut8-null (Fut8(-/-)) mice...
Ovarian low response to follicle-stimulating hormone (FSH) causes infertility featuring hypergonadotropic hypogonadism, ovarian failure, and/or defective response. N-glycosylation is essential for FSH receptor (FSHR). Core fucosylation catalyzed by fucosyltransferase 8 (FUT8) the most common N-glycosylation. level changes between individuals and plays important roles in multiple physiological pathological conditions. This study aims elucidate significance of FUT8 modulate FSHR function...
Abstract Fms‐like tyrosine kinase‐3 (FLT3) is a commonly mutated gene in acute myeloid leukemia (AML). The two most common mutations are the internal‐tandem duplication domain (ITD) mutation and kinase (TKD) mutation. FLT3‐ITD FLT3‐TKD exhibit distinct protein stability, cellular localization, intracellular signaling. To understand underlying mechanisms, we performed proximity labeling with TurboID to identify proteins that regulate or ‐TKD differently. We found BRCA1/BRCA2‐containing...
Fibronectin splice variants containing the EIIIA and/or EIIIB exons are prominently expressed in vasculature of a variety human tumors but not normal adult tissues. To understand functions these physiological and tumor angiogenesis, we used EIIIB-null EIIIA-null strains mice to examine neovascularization mouse retinas, pancreatic Rip-Tag transgenic mice, transplanted melanomas. Contrary expectations, angiogenesis was significantly affected by absence either or variants. Tumor growth also...
PTEN inactivation is the most frequent genetic aberration in endometrial cancer. One of phosphatase-independent roles associated with homologous recombination (HR) nucleus. Poly (ADP-ribose) polymerase (PARP) plays key repair DNA single-strand breaks, and a PARP inhibitor induces synthetic lethality cancer cells HR deficiency. We examined anti-tumor activity olaparib, inhibitor, its correlation between sensitivity status cell lines. The response to olaparib was evaluated using clonogenic...
Abstract An aberrant expression of integrin β1 has been implicated in breast cancer progression. Here, we compared the cell behaviors wild-type (WT), gene deleted (KO) and restored (Res) MDA-MB-231 cells. Surprisingly, exhibited opposite effects on proliferation. These were dependent densities they showed an up-regulation proliferation when cells cultured under sparse conditions a down-regulation growth dense conditions. By comparison with WT cells, phosphorylation levels ERK KO consistently...
Abstract The α2,3‐sialylation of N‐glycans is considered important but complicated because the functions three β‐galactoside α2,3‐sialyltransferases, ST3GAL3, ST3GAL4, and ST3GAL6, could be compensating for one another. To distinguish their specific functions, we established each individual knockout (KO) cell line. Loss either ST3GAL3 or ST3GAL6 genes decreased proliferation colony formation, as opposed to effect in ST3GAL4 KO cells. phosphorylation levels ERK AKT were significantly...
As an immune checkpoint, programmed cell death 1 (PD-1) and its ligand (PD-L1) pathway plays a crucial role in CD8+ cytotoxic T lymphocytes (CTL) activation provides antitumor responses. The N-glycans of PD-1 PD-L1 are highly core fucosylated, which solely catalyzed by the fucosyltransferase (Fut8). However, precise biological mechanisms underlying effects fucosylation on CTL have not been fully understood. In this study, we found that was significantly upregulated lung adenocarcinoma....
N-Acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of bisecting GlcNAc branch on N-glycans, is usually described as a metastasis suppressor. Overexpression GnT-III inhibited migration in multiple types tumor cells. However, these results seem controversial to clinical observations for increased expression human hepatomas, glioma, and ovarian cancers. Here, we present evidence that inconsistencies are mainly attributed different pattern cell sialylation. In detail,...