机构：[1]Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.[2]School of Life Sciences, Tsinghua University, Beijing 100084, China.[3]Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.外科系统胸外科首都医科大学宣武医院[4]School of Mechanical Engineering, Chengdu University, Chengdu 610000, China.[5]State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.[6]Shenzhen Bay Laboratory, Institute of Biomedical Health Technology and Engineering, Shenzhen 518055, China.
Cell communication and signal transduction rely heavily on the charge on the cell surface. The cell surface is negatively charged, with glycoproteins on the cell membrane providing a large percentage of the charge. Sialic acid is found on the outermost side of glycan chains and contributes to glycoprotein's negative charge. Sialic acid is highly expressed in tumor cells and plays an important role in tumor metastasis and immune escape by interacting with extracellular ligands. However, the specific effect of negative charge changes on glycoproteins is still poorly understood. In this study, we used 9-azido sialic acid (9Az-Sia) to create artificial epitopes on glycoproteins via metabolic glycan labeling, and we attached charged groups such as amino and carboxyl to 9Az-Sia via a click reaction with dibenzocyclooctyne (DBCO). The charge of glycoproteins was changed by metabolic glycan labeling and click modification. The results showed that the migration and invasion ability of the MDA-MB-231 cell labeled with 9Az-Sia was significantly reduced after the modification with amino groups rather than carboxyl groups. Epithelial-mesenchymal transition (EMT) is the biological process of metastatic tumor cells, with an increasing ability of tumor cells to migrate and invade. In particular, the expression of adhesion molecules increased in the amine-linked group, whereas the expression of matrix metalloproteinases (MMPs) increased significantly, which is not identical to EMT characteristics. In vivo experiments have demonstrated that the loss of negative charge on glycoproteins has an inhibitory effect on tumors. In conclusion, modifying the positive charge on the surface of glycoproteins can inhibit tumor cell metastasis and has great potential for tumor therapy.
基金：
This work was supported by the National Key R&D Program
of China (2020YFA0908900), the State Key Laboratory of
Chemical Oncogenomics, and the Institute of Biomedical
Health Technology and Engineering, Shenzhen Bay Laboratory.
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|2 区化学
小类|2 区生化研究方法2 区有机化学2 区化学：综合3 区生化与分子生物学
最新[2023]版：
大类|2 区化学
小类|2 区生化研究方法2 区有机化学3 区生化与分子生物学3 区化学：综合
JCR分区：
出版当年[2021]版：
Q1BIOCHEMICAL RESEARCH METHODSQ1BIOCHEMISTRY & MOLECULAR BIOLOGYQ1CHEMISTRY, ORGANICQ2CHEMISTRY, MULTIDISCIPLINARY
最新[2023]版：
Q1BIOCHEMICAL RESEARCH METHODSQ1CHEMISTRY, ORGANICQ2CHEMISTRY, MULTIDISCIPLINARYQ2BIOCHEMISTRY & MOLECULAR BIOLOGY
第一作者机构：[1]Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.[2]School of Life Sciences, Tsinghua University, Beijing 100084, China.
通讯作者：
通讯机构：[1]Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.[2]School of Life Sciences, Tsinghua University, Beijing 100084, China.[5]State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.[6]Shenzhen Bay Laboratory, Institute of Biomedical Health Technology and Engineering, Shenzhen 518055, China.
推荐引用方式(GB/T 7714)：
Wang Mingzhe,Kejian Shi,Ye Lei,et al.Transforms of Cell Surface Glycoproteins Charge Influences Tumor Cell Metastasis via Atypically Inhibiting Epithelial-Mesenchymal Transition Including Matrix Metalloproteinases and Cell Junctions[J].BIOCONJUGATE CHEMISTRY.2023,34(8):1498-1507.doi:10.1021/acs.bioconjchem.3c00303.
APA：
Wang Mingzhe,Kejian Shi,Ye Lei,Chen Jiaqi&Ma Lan.(2023).Transforms of Cell Surface Glycoproteins Charge Influences Tumor Cell Metastasis via Atypically Inhibiting Epithelial-Mesenchymal Transition Including Matrix Metalloproteinases and Cell Junctions.BIOCONJUGATE CHEMISTRY,34,(8)
MLA：
Wang Mingzhe,et al."Transforms of Cell Surface Glycoproteins Charge Influences Tumor Cell Metastasis via Atypically Inhibiting Epithelial-Mesenchymal Transition Including Matrix Metalloproteinases and Cell Junctions".BIOCONJUGATE CHEMISTRY 34..8(2023):1498-1507
