B4galt1, also known as beta-1,4-galactosyltransferase1, is a key gene involved in N-glycan biosynthesis. N-glycan biosynthesis is a crucial process that impacts the structure and function of many proteins, thus influencing various biological pathways and processes [1].

In lung adenocarcinoma, B4galt1 was highly expressed in invasive adenocarcinoma samples. Inhibition of B4galt1 in in vivo models increased CD8 + T-cell abundance and activity, enhancing the antitumour immunity of anti-PD-1 therapy. B4galt1 regulated LUAD cell proliferation and invasion both in vitro and in vivo, 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 stabilizes the TAZ protein via glycosylation, activating CD274 transcriptionally, leading to immune escape [1].

In hepatocellular carcinoma, decreased B4galt1 enhanced cell migration and invasion in vitro and promoted lung metastasis in NOD/SCID mice. B4galt1 downregulation altered N-glycosylation and enhanced the laminin-binding activity of integrin α6 and integrin β1 to promote invasiveness [2].

In glioblastoma, B4galt1 knockdown by lentivirus inhibited glioblastoma development in vitro and in vivo, increased apoptosis and autophagy [3].

In pancreatic ductal adenocarcinomas, high B4galt1 expression correlated with poor survival, and its depletion rescued the response of chemoresistant cells to gemcitabine in an orthotopic model. Mechanistically, elevated p65 activity up-regulated B4galt1, which then interacted with and stabilized CDK11p110 via N-linked glycosylation to promote cancer progression and chemoresistance [4].

In acute myeloid leukemia, B4galt1 was overexpressed, and silencing it significantly promoted apoptosis [5].

In conclusion, B4galt1 is essential in N-glycan biosynthesis and significantly impacts various disease conditions. Gene-knockout or knockdown models in different cancers such as lung adenocarcinoma, hepatocellular carcinoma, glioblastoma, pancreatic ductal adenocarcinomas, and acute myeloid leukemia have revealed its role in processes like cell proliferation, invasion, immune escape, apoptosis, and chemoresistance, offering potential therapeutic targets for these diseases.

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. 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/

3. 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/

4. 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/

5. 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/