中国肿瘤生物治疗杂志2025，Vol.32Issue(5)：469-475,7.DOI:10.3872/j.issn.1007-385x.2025.05.003
ST6GAL1通过激活Notch1/PI3K/AKT/mTORC1途径促进结直肠癌HCT116细胞糖酵解和迁移、侵袭
ST6GAL1 promotes glycolysis,migration and invasion of colorectal cancer HCT116 cells by activating the Notch1/PI3K/AKT/mTORC1 pathway
摘要
Abstract
Objective:To explore the effect of β-galactoside α-2-6sialyltransferase1(ST6GAL1)on glycolysis,migration and invasion of colorectal cancer(CRC)HCT116 cells and its possible molecular mechanisms.Methods:The difference in the expression of ST6GAL1 in CRC patients and healthy people was analyzed using the GEPIA2 database.WB was performed to detect the differences in the expressions of ST6GAL1 in CRC cell lines HCT116,SW480,Caco-2,HT29,LoVo and human normal colon epithelial cell line NCM460.The difference in the expressions of ST6GAL1 in CRC tissues and corresponding adjacent tissues was analyzed by immunohistochemistry.HCT116 cell lines with stably knocked down or overexpressed ST6GAL1 were constructed by lentivirus transfection.Cell migration ability was detected by scratch test.Cell invasion ability was detected by Transwell test.WB assay was performed to detect the expression levels of cell glycolysis-related proteins and Notch1 intracellular domain(Notch1 ICD)as well as the phosphorylation level of PI3K/AKT/mTOR pathway.The expression level of Notch1 ICD and its entry into nucleus were observed by immunofluorescence assay.The Notch1 receptor agonist Jagged1 was added to HCT116 cells,and the expression levels of glycolysis-related proteins and Notch1 ICD and PI3K/AKT/mTOR pathway phosphorylation level were detected by WB.Results:The expression of ST6GAL1 was up-regulated in CRC tissues and cells(all P<0.05).Compared with the control and overexpression groups,knockdown of ST6GAL1 resulted in significantly lower levels of Notch1 ICD expression and PI3K/AKT/mTORC1 phosphorylation in HCT116 cells,lower levels of cellular glycolysis-related protein expressions and weaker cell migration and invasion abilities(all P<0.05).Overexpression of ST6GAL1 increased Notch1 ICD expression levels within HCT116 cells and promoted their entry into the nucleus.Cell glycolysis-related protein expression levels were elevated(all P<0.05).Cell migration and invasion abilities were enhanced(all P<0.05).Conclusion:ST6GAL1 activates the PI3K/AKT/mTORC1 pathway through activation of Notch1 receptor and phosphorylation,thus enhancing the glycolytic level and migration and invasion abilities of CRC cells.关键词
β-半乳糖苷α-2-6唾液酸转移酶1/结直肠癌/HCT116细胞/Notch1/糖酵解/迁移/侵袭Key words
β-galactoside α-2-6sialyltransferase1(ST6GAL1)/colorectal cancer/HCT116 cell/Notch1/glycolysis/migration/invasion分类
临床医学引用本文复制引用
霍怡杉,吴会丽,段相冰,马秀敏,李涛..ST6GAL1通过激活Notch1/PI3K/AKT/mTORC1途径促进结直肠癌HCT116细胞糖酵解和迁移、侵袭[J].中国肿瘤生物治疗杂志,2025,32(5):469-475,7.基金项目
新疆维吾尔自治区天池英才青年博士项目(No.2025TCYCHYS) （No.2025TCYCHYS）
新疆维吾尔自治区自然科学基金(No.2021D01C185) （No.2021D01C185）
