C1galt1, also known as Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1, is a key glycosyltransferase in the O-glycosylation process. It is essential for synthesizing the core 1 structure of mucin-type O-glycans, a crucial post-translational modification. O-glycosylation is involved in numerous biological functions, such as angiogenesis, platelet production, and kidney development [1].

In cancer, C1galt1 has been the focus of many studies. In colon cancer cells, suppression of C1galt1 expression led to changes in protein glycosylation of cell membrane proteins, reducing cancer cell proliferation, adhesion, migration, and colony-forming ability. It also affected galectin-3-mediated tumour cell-cell interaction and MGL-mediated macrophage-tumour cell interaction [2]. In pancreatic ductal adenocarcinoma, C1galt1 knockdown using siRNA suppressed cell viability, migration, invasion, and increased gemcitabine sensitivity. In subcutaneous and pancreatic orthotopic injection models in NOD/SCID mice, C1galt1 knockdown decreased tumour growth and metastasis [4]. In glioblastoma, downregulation of C1galt1 suppressed cell proliferation, invasion, and migration in vitro and inhibited tumour growth in nude mice. It decreased the level of terminal galactose O-glycosylation and phosphorylation on epidermal growth factor receptor (EGFR), attenuated AKT/ERK phosphorylation, and decreased the expression of cyclinD1 and MMP9 through the AKT/ERK signaling pathway [3].

In conclusion, C1galt1 is vital for O-glycosylation and thus for various biological functions. Through gene-knockout or knockdown models in vivo, its role in cancer progression has been revealed, showing that it affects cell-cell interactions, cell viability, migration, invasion, and response to drugs in different cancers. These findings suggest C1galt1 could be a potential therapeutic target in cancer treatment [2,3,4].