ST6Gal2 promotes α2,6-sialylation and aggressive phenotypes in neuroblastoma cells

Neuroblastoma, a common solid tumor in childhood, can range from spontaneous regression to lethal, treatment-resistant disease. Researchers have found that abnormal 2,6-sialylation, a process involving the addition of sialic acid to glycoproteins, contributes to aggressive features in many cancers. However, the role of ST6Gal2, a neural-enriched 2,6-sialyltransferase, in neuroblastoma has not been extensively studied.

To investigate this, a team examined two large public cohorts containing 1,147 patients. They discovered that high ST6GAL2 expression was linked to significantly poorer overall and event-free survival in both cohorts. Moreover, ST6GAL2 expression was elevated in high-risk and MYCN-amplified tumors, varied across different International Neuroblastoma Staging System stages, and correlated positively with a mesenchymal transcriptional signature.

This correlation was consistent across both cohorts. The team also found that stable shRNA-mediated knockdown of ST6GAL2 in SK-N-AS and SK-N-BE(2) cells reduced cell proliferation and viability, impaired wound closure, and decreased migration and invasion. Preliminary experiments in SK-N-AS cells suggested that ST6GAL2 knockdown reduced binding of Sambucus nigra agglutinin, indicating a role for ST6Gal2 in 2,6-sialylation.

The findings suggest that ST6Gal2 expression is associated with aggressive clinical and transcriptional features and pro-tumorigenic phenotypes in neuroblastoma, making ST6Gal2-mediated sialylation a potential candidate pathway for further investigation.