ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 (ST8SIA1)

ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 (ST8SIA1), commonly known as GD3 synthase, is a Golgi-resident type II membrane protein and a key enzyme in the ganglioside biosynthetic pathway. It specifically catalyzes the transfer of sialic acid from CMP-sialic acid to the ganglioside GM3, resulting in the formation of GD3 and GT3, which are critical components of the cell membrane involved in cell-cell recognition and signal transduction. ST8SIA1 is significantly overexpressed in several aggressive cancers, including melanoma, glioblastoma, and triple-negative breast cancer, where the resulting accumulation of GD3 promotes tumor cell proliferation, migration, and survival by modulating pathways such as c-Met and FAK/AKT. Due to its role in oncogenesis and its relatively restricted expression in normal tissues, ST8SIA1 has emerged as a promising therapeutic target. Current drug development efforts include the creation of antibody-drug conjugates (ADCs) and small-molecule inhibitors designed to disrupt its enzymatic activity or downregulate its expression, thereby inhibiting pro-tumorigenic signaling and sensitizing cancer cells to other therapies like immunotherapy.

Other names

ST8GD3SSIAT8SIAT8-ASIAT8AST8SiaIAlpha-2,8-sialyltransferase 8AGanglioside GD3 synthaseGanglioside GT3 synthase

Catalyzes the transfer of sialic acid from CMP-sialic acid to the ganglioside GM3 to produce gangliosides GD3 and GT3; modulates pro-tumorigenic signaling pathways such as c-Met and FAK/AKT.