Alpha-N-acetylneuraminide alpha-2,8-sialyltransferase 1 (ST8SIA1)

Alpha-N-acetylneuraminide alpha-2,8-sialyltransferase 1 (ST8SIA1) is a type II transmembrane enzyme in the glycosyltransferase 29 family that catalyzes the addition of sialic acid in an alpha-2,8 linkage to GM3 to synthesize complex gangliosides, most notably GD3 and GT3[1][6]. ST8SIA1 activity is essential for the formation of b- and c-series gangliosides, and the resulting gangliosides (GD3, GD2) act as tumor-associated carbohydrate antigens highly expressed in neuroectodermal cancers and implicated in cancer cell migration, invasion, EMT, and stemness[1][7]. ST8SIA1 is mostly expressed during embryonic development, with low expression in adult tissues (mainly in the nervous system), but is re-expressed or upregulated in various cancers. Experimental inhibition of ST8SIA1 impairs cancer stem cell properties, tumorigenesis, and metastasis, making it an emerging therapeutic target in aggressive, treatment-resistant malignancies[1][7][2][3].

Other names

Ganglioside GD3 synthaseGanglioside GT3 synthaseGD3SAlpha-2,8-sialyltransferase 8ASialyltransferase 8ASialyltransferase St8Sia ISIAT8SIAT8ASIAT8-AST8SiaIalpha-N-acetylneuraminide alpha-2,8-sialyltransferaseEC 2.4.99.8Disialoganglioside synthaseGanglioside-specific alpha-2,8-polysialyltransferase

Inhibitors (e.g., siRNA) reduce formation of GD3 and downstream GD2, impairing cancer stem cell survival and metastasis[1][7] Targeting reduces cellular processes such as proliferation, migration, invasion, and cancer stemness by altering ganglioside biosynthetic pathways[7][1]