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

Abstract

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.

Membranous S100A10 Involvement in the Tumor Budding of Colorectal Cancer During Oncogenesis: Report of Two Cases with Immunohistochemical Analysis

“…Previous studies reported the association between the mutations of RAS oncogene, especially KRAS, and high frequency of TB [8,30]. S100A10 is also considered to contribute to ECM degradation as well as cancer development, invasion, and metastasis via cell surface plasmin generation and RAS cooperation, including KRAS [11,12,17]. A few studies reported the relationship between S100A10 and Wnt pathway [31], whereas a recent study suggested that S100A10 is a key regulator of the plasminogen activation system during TGF-β-induced EMT [20].…”

“…However, the reason why the protein complex is highly expressed in TB/PDC remains unclear, indicating the collapse of the cell polarity. In poorly differentiated cancer cells, the functions of S100A10-ANX A2 heterocomplex are out of balance and that another function, such as promotion of cell migration/invasion [11,12,23,35,38,40], becomes dominant. Hence, future studies will be necessary to con rm the aforementioned research question.…”

“…In conclusion, membranous S100A10 is related to TB of CRC during oncogenesis. This is possibly due to plasminogen activation, actin remodeling, and interaction with an altered ECM [17][18][19]34], and these functions are thought to be more predominant than ANX A2 [12][13][14][15][16][17][18]. However, further study is required to con rm this hypothesis.…”

Membranous S100A10 involvement in the tumor budding of colorectal cancer during oncogenesis: report of two cases with immunohistochemical analysis

“…Furthermore, changes in the expressions and/or functions of the S100 proteins are key steps in cancer development or progression [ 10 ]. S100A10, a member of the S100 protein family, is also expressed in various cells, including cancer cells [ 11 , 12 ]. S100A10 forms a heterocomplex with cytoplasmic annexin A2 (ANX A2), then translocates to the cell membrane from the cytoplasm, and plays various roles in cell dynamics [ 11 , 12 ].…”

“…S100A10, a member of the S100 protein family, is also expressed in various cells, including cancer cells [ 11 , 12 ]. S100A10 forms a heterocomplex with cytoplasmic annexin A2 (ANX A2), then translocates to the cell membrane from the cytoplasm, and plays various roles in cell dynamics [ 11 , 12 ]. It is well known that the S100A10-ANX A2 heterocomplex functions as a plasminogen receptor and promotes cell migration/invasion [ 11 – 17 ].…”