Critical role and its underlying molecular events of the plasminogen receptor, S100A10 in malignant tumor and non-tumor diseases.

S100A10 is a small molecular weight protein expressed in the cytoplasm of many cells and one of the members of the S100 protein family that binds calcium and forms the largest subgroup of EF-hand proteins. The regulatory processes of S100A10 are complicated. S100A10 participates in the regulation of a variety of tumor and non-tumor diseases through cascade reactions with multitudinous signaling molecules. In malignant tumors, such as acute promyelocytic leukemia (APL) and lung cancer, S100A10 is likely involved in their progression, including invasion and metastasis through the regulation of plasmin production and subsequent plasmin-dependent stimulation of other proteases, such as matrix metalloproteinase (MMP)-2 and -9. Both the plasmin and MMPs are capable of inducing degradation of the extracellular matrix (ECM) and basement membrane, which is a critical step for tumor progression. In non-tumor diseases, the distribution of S100A10 in the brain and its interaction with 5-hydroxytryptamine 1B (5-HT1B) receptor, an important mediator in the central nervous system that maintains a dynamic balance of the neurotransmitters, correlates with depression-like behavior. S100A10 also participates in inflammatory responses through the regulation of peripheral macrophage migration to the inflammatory sites, which depends on the generation of plasmin and other proteinases at the surface of macrophages. Considerable attention should be paid to understand the significant role of S100A10 in the modulation of malignant tumor and non-tumor diseases.