B4galt1, also known as beta-1,4-galactosyltransferase1, is a key gene involved in N-glycan biosynthesis. N-glycans play crucial roles in various cellular processes such as protein folding, cell-cell recognition, and signaling pathways [1,2,3].

In lung adenocarcinoma, B4galt1 is highly expressed in invasive adenocarcinoma samples. Knockdown of B4galt1 in in vitro and in vivo models showed that it regulated cell proliferation, invasion, and was related to the impaired antitumour capacity of CD8 + T cells. Mechanistically, it directly mediates the N-linked glycosylation of PD-L1 protein, preventing its degradation, and also stabilizes the TAZ protein via glycosylation, activating CD274 transcriptionally, leading to immune escape. Inhibition of B4galt1 increased CD8 + T-cell abundance and activity and enhanced anti-PD-1 therapy's antitumour immunity [1].

In hepatocellular carcinoma, decreased B4galt1 enhanced cell migration, invasion, and lung metastasis in NOD/SCID mice. B4galt1 knockdown increased cell adhesion to laminin by modifying integrins α6 and β1 N-glycans, promoting HCC cell invasiveness [3].

In glioblastoma, B4galt1 knockdown by lentivirus inhibited glioblastoma development in vitro and in vivo, increased apoptosis and autophagy [4].

In pancreatic ductal adenocarcinomas, genetic perturbation of B4galt1 expression in cell lines regulated cancer progression and chemoresistance. Depletion of B4galt1 rescued chemoresistant cells' response to gemcitabine in an orthotopic model [5].

In acute myeloid leukemia, silencing B4galt1 significantly promoted apoptosis [6].

In conclusion, B4galt1 plays diverse and significant roles in multiple diseases, mainly through its function in N-glycan biosynthesis which impacts cell-related processes such as proliferation, invasion, apoptosis, and immune evasion. Studies using gene knockdown or knockout models in these disease areas have provided valuable insights into the mechanisms underlying these diseases, potentially guiding the development of novel therapeutic strategies targeting B4galt1.

References:

1. Cui, Yanan, Li, Jun, Zhang, Pengpeng, Zhang, Erbao, Guo, Renhua. 2023. B4GALT1 promotes immune escape by regulating the expression of PD-L1 at multiple levels in lung adenocarcinoma. In Journal of experimental & clinical cancer research : CR, 42, 146. doi:10.1186/s13046-023-02711-3. https://pubmed.ncbi.nlm.nih.gov/37303063/

2. Hsu, Tzu-Hui, Chang, Yu-Chan, Lee, Yi-Yuan, Liu, Fu-Tong, Lin, Kuo-I. 2024. B4GALT1-dependent galectin-8 binding with TGF-β receptor suppresses colorectal cancer progression and metastasis. In Cell death & disease, 15, 654. doi:10.1038/s41419-024-07028-3. https://pubmed.ncbi.nlm.nih.gov/39231945/

3. Chen, Po-Da, Liao, Ying-Yu, Cheng, Yu-Chia, Wu, Yao-Ming, Huang, Min-Chuan. 2023. Decreased B4GALT1 promotes hepatocellular carcinoma cell invasiveness by regulating the laminin-integrin pathway. In Oncogenesis, 12, 49. doi:10.1038/s41389-023-00494-y. https://pubmed.ncbi.nlm.nih.gov/37907465/

4. Wang, Pu, Li, Xiaolong, Xie, Yuan. . B4GalT1 Regulates Apoptosis and Autophagy of Glioblastoma In Vitro and In Vivo. In Technology in cancer research & treatment, 19, 1533033820980104. doi:10.1177/1533033820980104. https://pubmed.ncbi.nlm.nih.gov/33287670/

5. Chen, Yitian, Su, Liangping, Huang, Cheng, Liu, Chao, Wong, Ping-Pui. 2020. Galactosyltransferase B4GALT1 confers chemoresistance in pancreatic ductal adenocarcinomas by upregulating N-linked glycosylation of CDK11p110. In Cancer letters, 500, 228-243. doi:10.1016/j.canlet.2020.12.006. https://pubmed.ncbi.nlm.nih.gov/33309857/

6. Ren, Zhihong, Huang, Xiaoyu, Lv, Qing, Wang, Fanping, Wang, Mingyong. 2022. High expression of B4GALT1 is associated with poor prognosis in acute myeloid leukemia. In Frontiers in genetics, 13, 882004. doi:10.3389/fgene.2022.882004. https://pubmed.ncbi.nlm.nih.gov/36568388/