S100 calcium-binding protein A4 (S100A4) (S100A4)

S100 calcium-binding protein A4 (S100A4), widely known by its alias Mts1 (Metastasin 1), is a member of the S100 family of EF-hand calcium-modulated proteins [1, 3, 5]. It is primarily recognized for its potent role in promoting cancer metastasis by enhancing cell motility, invasion, and angiogenesis [1, 4, 10]. S100A4 functions both intracellularly, by interacting with cytoskeletal components like non-muscle myosin IIA, and extracellularly, by signaling through receptors such as RAGE (Receptor for Advanced Glycation End-products) and TLR4 [11, 28, 29]. Beyond oncology, S100A4 is a key driver of tissue fibrosis in the liver, lungs, and kidneys, and it contributes to inflammatory conditions like rheumatoid arthritis [2, 4, 16]. Therapeutic strategies targeting S100A4 include small molecule inhibitors like niclosamide and sulindac, which suppress its transcription, and neutralizing antibodies like 6B12, which block its extracellular pro-metastatic activity [17, 18, 19, 24]. As a biomarker, elevated S100A4 levels in tumors or serum are often associated with poor prognosis and aggressive disease progression [1, 2, 4]. Given its involvement in multiple pathological processes, S100A4 represents a high-value target for preventing tumor progression and treating chronic fibrotic diseases [1, 3, 28].

Other names

Mts1Metastasin 1CAPLPEL98P9KA18A242AFSP1Fibroblast-specific protein 1

Inhibition of S100A4-mediated signaling (e.g., Wnt/beta-catenin, NF-kappaB, and ERK pathways), disruption of protein-protein interactions (e.g., with non-muscle myosin IIA or p53), and neutralization of extracellular S100A4 to prevent receptor-mediated activation [1, 2, 3, 11, 17, 19, 26, 29].