B4galt1, also known as beta-1,4-galactosyltransferase1, is a key gene involved in N-glycan biosynthesis [1]. N-glycan biosynthesis is associated with various cellular processes such as protein folding, cell-cell recognition, and immune response regulation. This gene's function is crucial in maintaining normal cellular functions and its dysregulation can lead to various biological consequences.

In lung adenocarcinoma, B4galt1 is highly expressed in invasive adenocarcinoma samples compared to minimally invasive adenocarcinoma. Knockdown of B4galt1 in in vitro and in vivo experiments showed that it regulated cell proliferation, invasion, and was related to the impaired antitumour capacity of CD8 + T cells. Mechanistically, it 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 expression was associated with enhanced cell migration, invasion, and lung metastasis. Knockdown or knockout of B4galt1 in HCC cells increased cell adhesion to laminin through modifying the N-glycans of integrins α6 and β1 [2].

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

In pancreatic ductal adenocarcinomas, genetic perturbation of B4galt1 expression in cell lines regulated cancer progression and chemoresistance. Depletion of B4galt1 rescued the response of chemoresistant cells to gemcitabine in an orthotopic model [4].

In acute myeloid leukemia, silencing B4galt1 significantly promoted apoptosis [5].

In conclusion, B4galt1 plays significant roles in multiple disease conditions, mainly through its function in N-glycan biosynthesis. Studies using gene knockdown or knockout models in various cancers such as lung adenocarcinoma, hepatocellular carcinoma, glioblastoma, pancreatic ductal adenocarcinomas, and acute myeloid leukemia have revealed its contribution to cancer cell proliferation, invasion, metastasis, immune escape, chemoresistance, and apoptosis regulation. These findings highlight B4galt1 as a potential therapeutic target in 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/