C1GALT1 high expression enhances the progression of glioblastoma through the EGFR-AKT/ERK cascade

被引:5
作者
Su, Yanting [1 ]
Ao, Xin [2 ]
Long, Yunfeng [2 ]
Zhang, Zhengrong [2 ]
Zhang, Mingzhu [2 ]
Zhang, Zhenwang [3 ]
Wei, Mingjie [2 ]
Shan, Shigang [1 ]
Lu, Surui [1 ]
Yu, You [1 ]
Xu, Bo [1 ]
机构
[1] Hubei Univ Sci & Technol, Sch Basic Med Sci, Xianning Med Colloge, Xianning 437100, Peoples R China
[2] Hubei Univ Sci & Technol, Sch Pharm, Xianning Med Coll, Xianning 437100, Peoples R China
[3] Hubei Univ Sci & Technol, Xianning Med Coll, Hubei Key Lab Diabet & Angiopathy, Xianning 437100, Peoples R China
基金
中国国家自然科学基金;
关键词
C1GALT1; Glycotransferase; O-glycosylation; Glioblastoma; EGFR; O-GLYCOSYLATION; CANCER; METASTASIS; SYSTEM; CELLS;
D O I
10.1016/j.cellsig.2024.111513
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Core1 beta 1,3-galactosyltransferase (C1GALT1) is an essential glycotransferase controlling the elongation of GalNAc-type O-glycosylation and its altered expression contributes tumor progression in various cancers. However, the mechanism how C1GALT1 influences gliomas remains unclear. Here,our results from The Cancer Genome Atlas (TCGA) database, The Chinese Glioma Genome Atlas (CGGA) database and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database showed that the expression of C1GALT1 was increased in higher grade gliomas namely glioblastoma compared with low grade gliomas or non-tumor tissues and significantly associated with poor survival. Downregulation of C1GALT1 suppressed cell proliferation, invasion, and migration in glioma cell lines. Consistent with the result in vitro, C1GALT1 knockdown distinctly inhibited the weight and tumor growth in nude mice. Mechanistically, C1GALT1 knockdown decreased the level of terminal galactose O-glycosylation and phosphorylation on epidermal growth factor receptor (EGFR). Moreover, The AKT/ERK phosphorylation was attenuated in C1GALT1 knockdown cells. And C1GALT1 knockdown decreased the expression of cyclinD1, matrix metalloproteinase 9 (MMP9) through the AKT/ERK signaling pathway Furthermore, transcription factor SP1 which the expression was found to be associated the C1GALT1 expression could bind to the promoter of C1GALT1 gene and regulated its expression. In conclusion, our data show that C1GALT1 enhances the progression of glioma by regulated the O-glycosylation and phosphorylation of EGFR and the subsequent downstream AKT/ERK signaling pathway. Therefore, C1GALT1 represents a potential target for the diagnosis and treatment of glioma.
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页数:12
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