Novel regulatory mechanisms of N-glycan sialylation: Implication of integrin and focal adhesion kinase in the regulation

• Published in: Biochimica et biophysica acta. General subjects Vol. 1868; no. 6; p. 130617
• Main Authors: Isaji, Tomoya, Gu, Jianguo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2024
• Subjects: Animals; FAK; Focal Adhesion Protein-Tyrosine Kinases - metabolism; gene expression; glycoproteins; glycosyltransferases; Golgi apparatus; Golgi Apparatus - metabolism; Humans; Integrin; integrins; Integrins - metabolism; N-glycan; neoplasm progression; non-specific protein-tyrosine kinase; PI4KIIα; Polysaccharides - metabolism; Sialylation; Sialyltransferase; Sialyltransferases - metabolism; therapeutics; ST; ST6GAL1; PI4KIIα; EGF; GORAB; CDG; Sialyltransferase; sLe; GnT-III; iPS; PI4P; FAK; GOLPH3; Integrin; PI3K; PI4K; miRNA; N-glycan; TGN; Sialylation; sialyl Tn; ST6GALNAC4; ST3GAL3
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2024.130617

Sialylation of glycoproteins, including integrins, is crucial in various cancers and diseases such as immune disorders. These modifications significantly impact cellular functions and are associated with cancer progression. Sialylation, catalyzed by specific sialyltransferases (STs), has traditionally been considered to be regulated at the mRNA level. Recent research has expanded our understanding of sialylation, revealing ST activity changes beyond mRNA level variations. This includes insights into COPI vesicle formation and Golgi apparatus maintenance and identifying specific target proteins of STs that are not predictable through recombinant enzyme assays. This review summarizes that Golgi-associated pathways largely influence the regulation of STs. GOLPH3, GORAB, PI4K, and FAK have become critical elements in sialylation regulation. Some STs have been revealed to possess specificity for specific target proteins, suggesting the presence of additional, enzyme-specific regulatory mechanisms. This study enhances our understanding of the molecular interplay in sialylation regulation, mainly focusing on the role of integrin and FAK. It proposes a bidirectional system where sialylations might influence integrins and vice versa. The diversity of STs and their specific linkages offer new perspectives in cancer research, potentially broadening our understanding of cellular mechanisms and opening avenues for new therapeutic approaches in targeting sialylation pathways. •Epigenetic and transcriptional factors influence ST gene expressions.•GOLPH3 and GORAB regulate sialylation through their roles in COPI vesicles.•FAK modulates the stability of PI4KIIα, influencing N-glycan sialylation.•ST6GAL1 and the ST3GAL family have distinct target substrates.