S100A10, also known as p11, is a multifunctional protein belonging to the S100 family of Ca2+-binding proteins, though it itself does not bind Ca2+ [8]. It commonly forms a heterotetrameric complex with Annexin A2, which is essential for the activation of the plasminogen activation pathway, leading to the generation of plasmin from plasminogen. This pathway is involved in various physiological processes such as fibrinolysis, angiogenesis, wound healing, as well as pathological processes like tumor progression [2,3,4,5,6,7].

In cancer research, S100A10 has been found to play significant roles. In hepatocellular carcinoma (HCC), S100A10 promotes HCC initiation, self-renewal, chemoresistance, and metastasis both in vitro and in vivo. It is secreted by HCC cells into extracellular vesicles (EVs), and these S100A10-enriched EVs enhance the stemness and metastatic ability of HCC cells, upregulate certain signaling pathways, and promote epithelial-mesenchymal transition. Blockage of EV-S100A10 with a neutralizing antibody significantly abrogates these enhancing effects [1]. In lung cancer metastasis research, S100A10-deficient mice showed reduced cancer metastasis in the lung. Activation of S100A10 within lung fibroblasts via tumor-derived exosomes increased the expression of certain chemokines, leading to the recruitment of myeloid-derived suppressor cells (MDSCs), and S100A10 inhibitors could block lung metastasis in vivo [9].

In conclusion, S100A10 is crucial in the plasminogen activation pathway and has a significant impact on cancer-related processes. Studies using gene-knockout models, such as S100A10-deficient mice, have revealed its role in cancer metastasis and the regulation of the immune microenvironment, providing potential therapeutic targets for cancer treatment, especially in HCC and lung cancer metastasis [1,9].