ST6Gal1, also known as β-galactosidase α2,6 sialyltransferase 1, is a Golgi-sialyltransferase. It adds negatively charged sialic acid to the terminal galactose of N-glycosylated proteins [1]. Its activity impacts various oncogenic signaling pathways. Upregulation of ST6Gal1 is associated with many malignancies, and it influences cancer hallmarks such as sustained proliferation, self-renewal, epithelial-to-mesenchymal transition, invasion, and chemoresistance [1]. Genetic models, like KO/CKO mouse models, can be valuable for further exploring its functions.

In pancreatic cancer, a GEM model with transgenic expression of ST6Gal1 in the pancreas showed that ST6Gal1 promoted acinar to ductal metaplasia (ADM) and accelerated PDAC progression. ST6Gal1-mediated sialylation activated EGFR, a key driver of ADM [2]. In rectal cancer, organoid models with ST6Gal1 knockdown had increased sensitivity to chemoradiation, indicating ST6Gal1 is associated with resistance to treatment in human rectal cancer [4]. In hepatocellular carcinoma, overexpression of ST6Gal1 in HCC cells inhibited migration and invasion in vitro and suppressed metastasis in vivo, suggesting it may act as a metastasis suppressor [3].

In conclusion, ST6Gal1 plays a crucial role in cancer-related biological processes. Through model-based research, especially KO/CKO mouse models in pancreatic, rectal, and hepatocellular carcinoma, we've gained insights into its functions. In cancer, ST6Gal1 can either promote or inhibit tumor progression depending on the cancer type, highlighting its complex role in disease development.

References:

1. Gc, Sajina, Bellis, Susan L, Hjelmeland, Anita B. 2022. ST6Gal1: Oncogenic signaling pathways and targets. In Frontiers in molecular biosciences, 9, 962908. doi:10.3389/fmolb.2022.962908. https://pubmed.ncbi.nlm.nih.gov/36106023/

2. Bhalerao, Nikita, Chakraborty, Asmi, Marciel, Michael P, Buchsbaum, Donald J, Bellis, Susan L. 2023. ST6GAL1 sialyltransferase promotes acinar to ductal metaplasia and pancreatic cancer progression. In JCI insight, 8, . doi:10.1172/jci.insight.161563. https://pubmed.ncbi.nlm.nih.gov/37643018/

3. Zou, Xia, Lu, Jishun, Deng, Yao, Gao, Chunfang, Zhang, Yan. 2022. ST6GAL1 inhibits metastasis of hepatocellular carcinoma via modulating sialylation of MCAM on cell surface. In Oncogene, 42, 516-529. doi:10.1038/s41388-022-02571-9. https://pubmed.ncbi.nlm.nih.gov/36528750/

4. Smithson, Mary, Diffalha, Sameer Al, Irwin, Regina K, Bellis, Susan L, Hardiman, Karin M. 2024. ST6GAL1 is associated with poor response to chemoradiation in rectal cancer. In Neoplasia (New York, N.Y.), 51, 100984. doi:10.1016/j.neo.2024.100984. https://pubmed.ncbi.nlm.nih.gov/38467087/