S100 calcium binding protein A4 (S100A4)

S100 calcium binding protein A4 (S100A4) is a small, cytoplasmic and nuclear protein of the S100 family characterized by two EF-hand calcium-binding motifs. It is involved in a variety of cellular processes, including regulation of cell cycle progression, cell motility, invasion, differentiation, and apoptosis. S100A4 acts via both intracellular and extracellular mechanisms, interacting with cytoskeletal proteins (e.g., nonmuscle myosin II, actin, tropomyosin) to regulate cell motility and invasiveness, and stimulating angiogenesis through extracellular signaling, particularly by synergizing with vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Overexpression and altered regulation of S100A4 are strongly associated with the acquisition of metastatic potential in cancer and poor patient prognosis. It is used as a diagnostic and prognostic biomarker for metastasis in several tumor types, most notably breast cancer. While a promising therapeutic target, direct clinical inhibitors are limited, with monoclonal antibodies like 5C3 under preclinical investigation[1][2][3][4].

Other names

Protein S100-A4CAPLMTS1P9KA18A2PEL9842AFSP1CalvasculinMetastasinPlacental calcium-binding proteinfibroblast-specific protein-1

Inhibition of extracellular S100A4 blocks angiogenesis, tumor progression, and cell migration (as demonstrated by monoclonal antibodies in xenograft models)[1].