C1galt1, also known as Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1 or Core 1β1,3-galactosyltransferase (C1GALT1), is a key glycosyltransferase in the O-glycosylation process. It is essential for synthesizing the core 1 structure of mucin-type O-glycans. O-glycosylation, a significant post-translational modification, along with N-glycosylation, plays a crucial role in regulating protein function. C1galt1 is involved in multiple biological functions such as angiogenesis, platelet production, and kidney development [1].

In cancer research, loss-of-function experiments on C1galt1 have shown its diverse roles. For example, in colorectal cancer, C1galt1 is central to the O-glycosylation process, producing tumor-associated carbohydrate antigens like Tn and sTn, which are linked to cancer metastasis and poor prognosis. The interaction between C1galt1 and core 3 synthase is crucial for gastrointestinal health, and its aberration can lead to CRC development [2]. In pancreatic ductal adenocarcinoma, C1galt1 knockdown using siRNA suppressed cell viability, migration, invasion, and increased gemcitabine sensitivity. High expression of C1galt1 was associated with poor disease-free and overall survival [7]. In gastric cancer, C1galt1 overexpression promoted cell proliferation, migration, and invasion due to the increase in O-glycan T antigen [8]. In glioblastoma, downregulation of C1galt1 suppressed cell proliferation, invasion, and migration both in vitro and in vivo [6]. In lung adenocarcinoma, C1galt1 promoted cell proliferation, migration, and invasion, and tumor formation in vivo [5]. In neuroblastoma, downregulation of C1galt1 promoted malignant behaviors in vitro and in vivo, while its high expression predicted a favorable prognosis [3]. In colon cancer cells, suppression of C1galt1 expression led to significant reduction of cancer cell proliferation, adhesion, migration, and the ability to form colonies [4].

In conclusion, C1galt1 is essential for O-glycosylation and plays a vital role in various biological functions. Model-based research, especially loss-of-function experiments, has revealed its significant roles in cancer development and progression across multiple cancer types, highlighting its potential as a therapeutic target.

References:

1. Sun, Xiaojie, Zhan, Mengru, Sun, Xun, Liu, Wanqi, Meng, Xiangwei. 2021. C1GALT1 in health and disease. In Oncology letters, 22, 589. doi:10.3892/ol.2021.12850. https://pubmed.ncbi.nlm.nih.gov/34149900/

2. Tian, Hong, Yu, Jia-Li, Chu, Xiaoli, Liu, Juan, Liu, Ying. 2024. Unraveling the role of C1GALT1 in abnormal glycosylation and colorectal cancer progression. In Frontiers in oncology, 14, 1389713. doi:10.3389/fonc.2024.1389713. https://pubmed.ncbi.nlm.nih.gov/38699634/

3. Lin, Neng-Yu, Chen, Syue-Ting, Chang, Hsiu-Ling, Huang, Min-Chuan, Chang, Hsiu-Hao. 2022. C1GALT1 expression predicts a favorable prognosis and suppresses malignant phenotypes via TrkA signaling in neuroblastoma. In Oncogenesis, 11, 8. doi:10.1038/s41389-022-00383-w. https://pubmed.ncbi.nlm.nih.gov/35169131/

4. Wan, Yangu, Adair, Kareena, Herrmann, Anne, Duckworth, Carrie A, Yu, Lu-Gang. 2023. C1GalT1 expression reciprocally controls tumour cell-cell and tumour-macrophage interactions mediated by galectin-3 and MGL with double impact on cancer development and progression. In Cell death & disease, 14, 547. doi:10.1038/s41419-023-06082-7. https://pubmed.ncbi.nlm.nih.gov/37612278/

5. Dong, Xiaoxia, Liu, Yongyu, Deng, Xinzhou, Chen, Chunli, Shen, Li. 2021. C1GALT1, Negatively Regulated by miR-181d-5p, Promotes Tumor Progression via Upregulating RAC1 in Lung Adenocarcinoma. In Frontiers in cell and developmental biology, 9, 707970. doi:10.3389/fcell.2021.707970. https://pubmed.ncbi.nlm.nih.gov/34307388/

6. Su, Yanting, Ao, Xin, Long, Yunfeng, Yu, You, Xu, Bo. 2024. C1GALT1 high expression enhances the progression of glioblastoma through the EGFR-AKT/ERK cascade. In Cellular signalling, 125, 111513. doi:10.1016/j.cellsig.2024.111513. https://pubmed.ncbi.nlm.nih.gov/39561885/

7. Kuo, Ting-Chun, Wu, Ming-Hsun, Yang, Shih-Hung, Tien, Yu-Wen, Huang, Min-Chuan. 2021. C1GALT1 high expression is associated with poor survival of patients with pancreatic ductal adenocarcinoma and promotes cell invasiveness through integrin αv. In Oncogene, 40, 1242-1254. doi:10.1038/s41388-020-01594-4. https://pubmed.ncbi.nlm.nih.gov/33420364/

8. Bao, Xiaojuan, Yu, Hanjie, Chen, Zhuo, Wu, Xin, Li, Zheng. 2024. C1GALT1-mediated O-glycan T antigen increase enhances the migration and invasion ability of gastric cancer cells. In Biochemical and biophysical research communications, 734, 150641. doi:10.1016/j.bbrc.2024.150641. https://pubmed.ncbi.nlm.nih.gov/39243676/