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ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 4 (ST8SIA4)

Target: ST8SIA4
Molecular classification: Enzyme, Glycosyltransferase (specifically, glycosyltransferase family 29)[2], Type II membrane protein[2]

Overview

ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 4 (ST8SIA4) is an enzyme that catalyzes the transfer of sialic acid residues to alpha-2,8-linked positions on glycoproteins, primarily generating polysialic acid—a crucial modulator of neural cell adhesion molecule (NCAM1) function. It is a member of the glycosyltransferase family 29 and is primarily located in the Golgi apparatus as a type II membrane protein[1][2][6]. ST8SIA4 has an essential role in regulating cell-cell adhesion in neural tissues and is implicated in various developmental and disease processes, including tumor progression, metastasis, and chemoresistance in certain cancers[5].

Other names: CMP-N-acetylneuraminate-poly-alpha-2,8-sialyltransferasePSTPST-1ST8Sia IVSialyltransferaseSIAT8-DST8SIA-IVST8 α-N-acetyl-neuraminide α-2,8-sialyltransferase 4LOC501189[1][2]

Mechanism of action

Inhibition of ST8SIA4 would reduce polysialic acid synthesis, altering neural cell adhesion and potentially affecting tumor cell migration and invasion. Modulation of its activity impacts the PI3K/Akt signaling pathway in some cancer types (such as in chronic myeloid leukemia)[5]

Biological functions

Synthesis of polysialic acid[2][4]Modulation of neural cell adhesion molecule (NCAM1) adhesive properties[2]Cell-cell adhesion modulationNeural development

Disease associations

Cancer (linked to multidrug resistance, e.g., chronic myeloid leukemia via PI3K/Akt pathway)[5]Neurological/neurodevelopmental disorders (due to its role in neural cell adhesion and polysialic acid production)Other (implicated in cell proliferation and possibly metastasis)

Safety considerations

Inhibition could impair neural development or function due to its essential role in the nervous systemOff-target effects on normal cell adhesion in non-cancerous tissues

Biomarkers

Polysialic acid (product of this enzyme, used as a marker of ST8SIA4 activity)ST8SIA4 mRNA/protein expression (especially as a marker in cancer tissues)

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