The Multifaceted Roles of ST3GAL Family in Cancer: Mechanistic Insights and Therapeutic Implications

Abstract

Sialylation is a critical glycosylation process involving the covalent attachment of sialic acid residues to the terminal glycans of glycoproteins and glycolipids. This modification is predominantly mediated by sialyltransferases(STs), which play pivotal roles in cell signaling, immune response, and cellular adhesion and migration. Aberrant sialylation, resulting from dysregulated expression of STs, is a hallmark of cancer, frequently observed on the surfaces of both tumor and stromal cells.The ST3GAL family, a key subset of STs, facilitates α-2,3-sialylation and has emerged as a crucial regulator of tumor cell proliferation, motility, drug resistance, and the immunosuppressive tumor microenvironment. Despite its recognized significance, a comprehensive synthesis of the diverse roles and molecular mechanisms of the ST3GAL family in tumor progression is still lacking. This review consolidates current knowledge on the molecular structure, biological functions, and pathological implications of the ST3GAL family in cancer, with a focus on its roles in signal modulation, immune evasion, and therapeutic targeting. By highlighting its potential as a key player in oncogenic processes, this review aims to provide novel insights to inform future research and clinical applications.

Keywords: ST3GAL; Sialic Acid-Siglec axis; cancer progression; drug resistance; sialylation; tumor microenvironment.