ST6GALNAC1, an enzyme known as ST6 N-Acetylgalactosaminide Alpha-2,6-Sialyltransferase 1, is crucial for catalyzing the formation of sialyl Tn (sTn), a truncated O-glycan. This sialylation process is involved in multiple biological pathways and is of great biological importance, especially in cell-cell interactions and the regulation of mucus integrity [1,2]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, can provide valuable insights into its function.

In embryo implantation, inhibiting endometrial ST6GALNAC1/sTn via siRNAs and anti-sTn antibodies in mouse uterine horns at the pre-implantation stage significantly impaired embryo implantation. This shows that ST6GALNAC1-regulated sTn in the endometrium aids embryo attachment through interaction with trophoblastic Siglecs [1]. In intestinal mucus, mice harboring a patient-like ST6GALNAC1 mutation have compromised mucus barriers, dysbiosis, and susceptibility to intestinal inflammation, indicating ST6GALNAC1-mediated mucus sialylation is essential for intestinal host-commensal homeostasis [2]. In breast cancer cells, constructing ST6GALNAC1 knockoff cells using siRNA-containing plasmids showed that ST6GALNAC1 promotes cell migration and invasion via the epithelial-mesenchymal transition (EMT) pathway [3]. In ovarian cancer stem cells, silencing ST6GALNAC1 reduced cell proliferation, migration, invasion, self-renewal ability, and tumorigenicity, suggesting its stimulative role via the Akt signaling pathway [4].

In conclusion, ST6GALNAC1 is essential for various biological processes, including embryo implantation, maintaining intestinal mucus integrity, and is also involved in cancer-related processes such as cell migration, invasion, and stem-like cell phenotypes. The use of KO/CKO mouse models has been instrumental in revealing these functions in the context of embryo implantation, intestinal diseases, and cancer research.

References:

1. Dong, Xinyue, Wang, Hao, Cai, Jinxuan, Zhang, Jian V, Yu, Ming. 2024. ST6GALNAC1-mediated sialylation in uterine endometrial epithelium facilitates the epithelium-embryo attachment. In Journal of advanced research, , . doi:10.1016/j.jare.2024.07.021. https://pubmed.ncbi.nlm.nih.gov/39111624/

2. Yao, Yikun, Kim, Girak, Shafer, Samantha, Wu, Chuan, Lenardo, Michael J. 2022. Mucus sialylation determines intestinal host-commensal homeostasis. In Cell, 185, 1172-1188.e28. doi:10.1016/j.cell.2022.02.013. https://pubmed.ncbi.nlm.nih.gov/35303419/

3. Luo, Yunzhao, Cao, Heng, Lei, Chuqi, Liu, Jun. 2023. ST6GALNAC1 promotes the invasion and migration of breast cancer cells via the EMT pathway. In Genes & genomics, 45, 1367-1376. doi:10.1007/s13258-023-01445-y. https://pubmed.ncbi.nlm.nih.gov/37747641/

4. Wang, Wen-Yan, Cao, Yun-Xia, Zhou, Xiao, Zhan, Lei, Sun, Shi-Ying. 2019. Stimulative role of ST6GALNAC1 in proliferation, migration and invasion of ovarian cancer stem cells via the Akt signaling pathway. In Cancer cell international, 19, 86. doi:10.1186/s12935-019-0780-7. https://pubmed.ncbi.nlm.nih.gov/30996686/