St3gal4, also known as ST3 beta-galactoside alpha-2,3-sialyltransferase 4, is a sialyltransferase enzyme. It plays a crucial role in regulating cancer progression, immune cell recruitment, and viral adsorption by modifying glycoproteins through sialylation. It is involved in various biological pathways such as cell proliferation, aerobic glycolysis, and immune-related signaling. Genetic models, especially knockout models, are valuable for studying its functions [1-10].

In St3gal4-/-mice, there was a marked decrease in eosinophil extravasation and adhesion, reduced binding of chemokine CCL11 to eosinophils and its receptor CCR3, and almost absent CCR3 internalization in CCL11-stimulated eosinophils. In an ovalbumin-induced allergic airway disease model, St3gal4-deficient mice had a dramatic reduction in eosinophil numbers in bronchoalveolar lavage fluid. Also, tissue-resident eosinophil numbers in the thymus and adipose tissue were reduced in the absence of ST3Gal-IV [2]. In breast cancer cells, inhibiting St3gal4 expression decreased cell viability, disrupted cell cycle progression, and reduced aerobic glycolysis and lactate dehydrogenase A (LDHA) expression. Suppressing St3gal4 expression in animal models reduced tumor growth and cell proliferation [1]. In osteosarcoma cells, knockdown of St3gal4 significantly inhibited proliferation, migration, invasion, and glycolysis, and inhibited the M2 polarization of macrophages [3].

In conclusion, St3gal4 is essential in processes like eosinophil recruitment, tumorigenesis, and tumor-associated metabolism. Gene knockout models in mice have revealed its role in allergic diseases, breast cancer, and osteosarcoma, providing insights into potential therapeutic targets for these disease areas.