St3gal6, short for ST3 β -galactoside α2,3 -sialyltransferase 6, is a significant glycosyltransferase. It is responsible for adding α2,3 -linked sialic acid to substrates, generating glycan structures, and thus plays a role in sialylation, an essential form of glycosylation [2]. Sialylation is associated with multiple biological processes, and St3gal6 may be involved in pathways like PI3K/Akt, which are related to cancer progression and cell autophagy [1,2].

In multiple myeloma, knockdown of St3gal6 led to a significant reduction in levels of α -2,3 -linked sialic acid on the cell surface, along with decreased adhesion to bone marrow stromal cells and fibronectin, and reduced transendothelial migration in vitro. In vivo, it showed reduced homing and engraftment of St3gal6 -knockdown cells to the bone marrow niche, decreased tumor burden, and prolonged survival [5].

In hepatocellular carcinoma, upregulation of St3gal6 was found to correlate with cell proliferation, migration, and invasion ability, and miR -26a negatively regulated St3gal6, suppressing these cellular activities through the Akt/mTOR pathway [3].

In lung adenocarcinoma, deficiency of St3gal6 promoted cell invasiveness with activated EGFR/MAPK signaling [4].

In hepatic encephalopathy, silencing St3gal6 and blocking or degrading α2,3 -sialylated glycans inhibited autophagy, and St3gal6 regulated autophagy through the HSPB8-BAG3 complex [2].

In conclusion, St3gal6 plays crucial roles in multiple biological processes and disease conditions. Through gene-knockout or knockdown models, its functions in cancer cell behavior such as proliferation, migration, invasion, as well as in cell adhesion, autophagy, and related signaling pathways have been revealed. These findings contribute to understanding the mechanisms of diseases like multiple myeloma, hepatocellular carcinoma, lung adenocarcinoma, and hepatic encephalopathy, providing potential targets for treatment.