Our studies reveal that S100A16 overexpression triggers GC cells proliferation and migration both in vivo and in vitro; by contrast, S100A16 knockdown restricts the speed of GC cells growth and mobility. Proteomic analysis results reveal a large S100A16 interactome, which includes ZO-2 (Zonula Occludens-2), a master regulator of cell-to-cell tight junction