ST6Gal1, also known as βgalactosidase α2,6 sialyltransferase 1, is a Golgi-sialyltransferase. It adds sialic acid, a negatively charged sugar, to the terminal galactose of N-glycosylated proteins. Its function impacts various oncogenic signaling pathways, and it is involved in multiple cancer hallmarks, such as sustained proliferation, self-renewal, epithelial-to-mesenchymal transition, invasion, and chemoresistance [1].

In pancreatic cancer, ST6Gal1 was upregulated in early-stage patients and further increased in advanced disease. Tumor xenograft experiments with human PDAC cells and a genetically engineered mouse (GEM) model showed its tumor-promoting function. Mice with dual expression of ST6Gal1 and oncogenic KRASG12D had accelerated PDAC progression compared to those with KRASG12D alone. ST6Gal1 also promotes acinar to ductal metaplasia (ADM), a process that fosters neoplasia, and EGFR activation was increased in acinar cells from ST6Gal1-transgenic mice [2].

In rectal cancer, organoid models treated with chemoradiation showed increased ST6Gal1 mRNA and protein. Knockdown of ST6Gal1 in an organoid model increased Cleaved Caspase-3, indicating reduced resistance to apoptosis. In a tissue microarray, post-treatment ST6Gal1 staining was associated with a worse grade of treatment response [3].

In conclusion, ST6Gal1 is a key player in cancer, with its overexpression promoting tumor growth, invasion, and conferring chemoresistance in pancreatic and rectal cancer models. The use of GEM models and organoid models has been crucial in revealing these disease-associated functions of ST6Gal1, highlighting its potential as a therapeutic target in cancer treatment.