Review
Biochemistry & Molecular Biology
Kayla Bastian, Emma Scott, David J. Elliott, Jennifer Munkley
Summary: Aberrant glycosylation, particularly altered core fucosylation driven by FUT8, is a universal feature of cancer cells impacting tumor progression. Upregulated FUT8 plays critical roles in immune evasion and cancer development, outlining potential opportunities for future therapeutics targeting FUT8.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Geriatrics & Gerontology
Wen Zhang, Wenchao Lin, Xiaofang Zeng, Mengqiu Zhang, Qin Chen, Yiyang Tang, Jing Sun, Benhui Liang, Lihuang Zha, Zaixin Yu
Summary: This study explored the role of core fucosylation and the glycosyltransferase FUT8 in pulmonary arterial hypertension (PAH). The increased core fucosylation observed in PAH rat models and isolated rat pulmonary artery smooth muscle cells (PASMCs) was inhibited by 2-fluorofucose (2FF), which improved hemodynamics and pulmonary vascular remodeling. FUT8 expression and concentration were found to be elevated in PAH patients, and knockdown of FUT8 alleviated the phenotypic changes in PASMCs induced by PDGF-BB. FUT8 activated the AKT pathway and its effects on PASMCs could be partially counteracted by an AKT activator.
Article
Neurosciences
Lee-Way Jin, Jacopo di Lucente, Ulises Ruiz Mendiola, Xinyu Tang, Angela M. Zivkovic, Carlito B. Lebrilla, Izumi Maezawa
Summary: FUT8-catalyzed core fucosylation plays a significant role in microglial activation induced by amyloid-beta oligomer (AβO). Inhibition of fucosylation reduces the induction of pro-inflammatory cytokines and rectifies phagocytic deficits in AβO-stimulated microglia. FUT8 is a component of the p53 signaling cascade regulating microglial behavior.
Article
Biochemistry & Molecular Biology
Ruben Lopez-Cortes, Isabel Correa Pardo, Laura Muinelo-Romay, Almudena Fernandez-Briera, Emilio Gil-Martin
Summary: The inhibition of FucT-8 gene can enhance TRAIL-induced apoptosis in CRC cells, and core fucosylation can control the ERK/MAPK pro-survival pathway. Depletion of core fucosylation sensitizes primary tumour SW480 cells to the combination therapy of TRAIL and low doses of chemotherapeutic drugs, while enhances the resistance of FUT8-knockdown metastatic SW620 cells. FucT-8 could be a potential target for increasing apoptosis and drug response in early CRC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Gerard Cantero-Recasens, Carla Burballa, Yuki Ohkawa, Tomohiko Fukuda, Yoichiro Harada, Amy J. Curwin, Nathalie Brouwers, Gian A. Thun, Jianguo Gu, Ivo Gut, Naoyuki Taniguchi, Vivek Malhotra
Summary: The study reveals that FUT8 and specific mucin levels are increased in the distal inflamed colon of UC patients, and overexpression of FUT8 in colonic cells affects the secretion of MUC1, MUC2, and MUC5AC, thus modifying the biophysical properties of mucus.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Oncology
Chengcheng Liao, Jiaxing An, Suqin Yi, Zhangxue Tan, Hui Wang, Hao Li, Xiaoyan Guan, Jianguo Liu, Qian Wang
Summary: The research highlights the association between FUT8 and core fucosylation in various tumors, suggesting their potential as markers for cancer diagnosis and prognosis, as well as providing potential targets for tumor therapy. Additionally, defucosylation of IGg1 antibodies may enhance antibody affinity, presenting another avenue for tumor therapy utilizing FUT8.
Article
Cell Biology
Shanyi Lin, Lenian Zhou, Yang Dong, Qingcheng Yang, Quanjun Yang, Hanqiang Jin, Ting Yuan, Shumin Zhou
Summary: The study found that lower levels of FUT8 in osteosarcoma patients and cell lines are associated with the growth and progression of OS, with attenuated FUT8 expression leading to decreased levels of core-fucosylation of TNFRs, activating non-canonical NF-kappa B signaling pathway and reducing apoptosis in OS cells. FUT8 functions as a negative regulator of OS that enhances OS-cell apoptosis, suggesting a potential novel therapeutic strategy.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Cheng-Fen Tu, Fu-An Li, Ling-Hui Li, Ruey-Bing Yang
Summary: Core fucosylation mediated by FUT8 enhances signaling of TGF-beta receptor, promoting breast cancer invasion and metastasis. Quantitative glycoproteomics identified 140 common core-fucosylated target glycoproteins, while pathway analysis highlighted crucial signaling networks like core fucosylation of integrin alpha v beta 5 or IL6ST for breast cancer cell invasion and migration.
BREAST CANCER RESEARCH
(2022)
Article
Chemistry, Physical
Ana Garcia-Garcia, Sonia Serna, Zhang Yang, Ignacio Delso, Victor Taleb, Thomas Hicks, Raik Artschwager, Sergey Y. Vakhrushev, Henrik Clausen, Jesus Angulo, Francisco Corzana, Niels C. Reichardt, Ramon Hurtado-Guerrero
Summary: Core fucosylation by FUT8 is affected by the underlying peptide sequence for paucimannose and high-mannose N-glycans, but not for complex-type N-glycans. FUT8 recognizes all sugar units and most amino acid residues of the G0 N-glycan, with optimal recognition requiring prior binding to GDP-Fuc. Genetic engineering in CHO cells demonstrated that core fucosylation mainly occurs on complex-type N-glycans, but certain glycosites can acquire Fuc on high-mannose N-glycans.
Article
Multidisciplinary Sciences
Yun Huang, Hai-Liang Zhang, Zhi-Ling Li, Tian Du, Yu-Hong Chen, Yan Wang, Huan-He Ni, Kai-Ming Zhang, Jia Mai, Bing-Xin Hu, Jun-Hao Huang, Li-Huan Zhou, Dong Yang, Xiao-Dan Peng, Gong-Kan Feng, Jun Tang, Xiao-Feng Zhu, Rong Deng
Summary: The study demonstrates the aberrant glycosylation of B7H3 in triple-negative breast cancer tumors, with a potential for core fucosylation inhibitor and anti-PDL1 combination therapy to enhance therapeutic efficacy in B7H3-positive TNBC tumors as a promising strategy for improving anti-tumor immune responses.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Caixia Liang, Tomohiko Fukuda, Tomoya Isaji, Chengwei Duan, Wanli Song, Yuqin Wang, Jianguo Gu
Summary: FUT8 knockout inhibited cell migration and proliferation in pancreatic adenocarcinoma cell lines, reduced expression of cancer stemness markers, destabilized spheroid formations, and enhanced chemosensitivity to gemcitabine. This suggests that FUT8 may play a crucial role in regulating stemness features and could offer new insights for pancreatic carcinoma treatment.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Biotechnology & Applied Microbiology
Simon Joubert, Julie Guimond, Sylvie Perret, Felix Malenfant, S. Mehdy Elahi, Anne Marcil, Marie Parat, Michel Gilbert, Anne E. G. Lenferink, Jason Baardsnes, Yves Durocher
Summary: A method to enhance the effector function of antibodies and increase their antitumor activity by inhibiting core fucosylation is discussed. The expression of a membrane-associated anti-FUT8 intrabody in the endoplasmic reticulum and Golgi apparatus reduces FUT8 enzyme activity and core fucosylation of antibody N-glycans, resulting in antibodies with enhanced ADCC effector function.
BIOTECHNOLOGY AND BIOENGINEERING
(2022)
Article
Cell Biology
Mengmeng Wang, Zhoudong Zhang, Mengxi Chen, Yixin Lv, Sheng Tian, Fanyi Meng, Yawen Zhang, Xuqin Guo, Yinshuang Chen, Man Yang, Jiawei Li, Tian Qiu, Fang Xu, Zhi Li, Qi Zhang, Jie Yang, Jing Sun, Hongjian Zhang, Haiyang Zhang, Huanqiu Li, Weipeng Wang
Summary: Metastatic colorectal cancer (mCRC) lacks effective therapeutics, highlighting the need for new drugs. Fucosyltransferase 8 (FUT8) is highly expressed in CRC and mediates core fucosylation of CD276 (B7-H3), a key immune checkpoint molecule. The small-molecule inhibitor FDW028 targets FUT8 and demonstrates potent anti-tumor activity by defucosylation and lysosomal degradation of B7-H3. FUT8 inhibition destabilizes B7-H3 through chaperone-mediated autophagy, making FDW028 a promising therapeutic candidate for mCRC.
CELL DEATH & DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Yuki Ohkawa, Yoichiro Harada, Naoyuki Taniguchi
Summary: Glycosylation is a common posttranslational modification of proteins, regulated by various glycosyltransferases and glycosidases. The core fucose structure on N-glycans may have protective functions against emphysema and COPD. Glycomimetics using glycan analogs could be a promising therapeutic strategy for various medical conditions.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Biochemistry & Molecular Biology
Seita Tomida, Masamichi Nagae, Yasuhiko Kizuka
Summary: The FUT8 stem region is crucial for enzyme oligomerization. Loss of the stem region destabilizes the FUT8 protein structure, leading to altered cellular localization and shortened half-life, without affecting the catalytic activity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Tahir Mehmood, Amara Maryam, He Zhang, Yongming Li, Muhammad Khan, Tonghui Ma
Review
Medicine, General & Internal
Jingzhou Mu, Qiuyu Chen, Liang Zhu, Yunhong Wu, Suping Liu, Yufei Zhao, Tonghui Ma
CURRENT MEDICAL RESEARCH AND OPINION
(2019)
Article
Medicine, Research & Experimental
Yan Yang, Kai Xue, Zhi Li, Wei Zheng, Weijie Dong, Jiazhe Song, Shijie Sun, Tonghui Ma, Wenzhe Li
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2018)
Article
Mycology
L. F. Yang, X. Liu, L. L. Lv, Z. M. Ma, X. C. Feng, T. H. Ma
JOURNAL DE MYCOLOGIE MEDICALE
(2018)
Article
Cell Biology
Amara Maryam, Tahir Mehmood, Qiulong Yan, Yongming Li, Muhammad Khan, Tonghui Ma
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2018)
Article
Pharmacology & Pharmacy
Bo Yu, Yu Jiang, Bo Zhang, Hong Yang, Tonghui Ma
PHARMACOLOGICAL RESEARCH
(2018)
Article
Immunology
Wei Liang, Shanshan Mao, Shijie Sun, Ming Li, Zhi Li, Rui Yu, Tonghui Ma, Jianguo Gu, Jianing Zhang, Naoyuki Taniguchi, Wenzhe Li
FRONTIERS IN IMMUNOLOGY
(2018)
Article
Oncology
Zhuo Liu, Miao Yu, Bingyuan Fei, Xuedong Fang, Tonghui Ma, Dongxin Wang
Article
Physiology
Dejiang Wang, Xiangjun Di, Jie Wang, Miao Li, Di Zhang, Yaxin Hou, Jiao Hu, Ge Zhang, He Zhang, Meiyan Sun, Xiangyu Meng, Bo Sun, Chunlai Jiang, Tonghui Ma, Weiheng Su
FRONTIERS IN PHYSIOLOGY
(2018)
Article
Hematology
Mingcheng Liu, Qiwang Liu, Yandong Pei, Miaomiao Gong, Xiaolin Cui, Jinjin Pan, Yunlong Zhang, Yang Liu, Ying Liu, Xiaocheng Yuan, Haoran Zhou, Yiying Chen, Jian Sun, Lin Wang, Xiya Zhang, Rui Wang, Shao Li, Jizhong Cheng, Yanchun Ding, Tonghui Ma, Yuhui Yuan
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2019)
Article
Biotechnology & Applied Microbiology
Jie Wang, Miao Li, Xiaolin Cui, Dongyue Lv, Lingling Jin, Muhammad Khan, Tonghui Ma
ONCOTARGETS AND THERAPY
(2018)
Article
Biotechnology & Applied Microbiology
Longfei Yang, Xin Liu, Lili Zhong, Yujie Sui, Guihua Quan, Ying Huang, Fang Wang, Tonghui Ma
BIOMED RESEARCH INTERNATIONAL
(2018)
Article
Multidisciplinary Sciences
Jing Xu, Hebin Sun, Guoling Huang, Gang Liu, Zhi Li, Hui Yang, Lingling Jin, Xiaolin Cui, Lei Shi, Tonghui Ma, Akihiko Kameyama, Weijie Dong
SCIENTIFIC REPORTS
(2019)
Article
Biotechnology & Applied Microbiology
Longfei Yang, Xin Liu, Yujie Sui, Zhiming Ma, Xuechao Feng, Fang Wang, Tonghui Ma
BIOMED RESEARCH INTERNATIONAL
(2019)