Metastasis-Associated Protein S100A4: Spotlight on its Role in Cell Migration

Abstract

S100A4 (also known as Mts1, metastasin, p9Ka, pEL98, CAPL, calvasculin, Fsp-1, placental calcium-binding protein) belongs to the family of EF-hand calcium-binding proteins, whose expression is elevated in a number of pathological conditions. Although it is well documented that S100A4 is expressed in cancer cells and contributes to tumor cell motility and metastatic progression, the exact underlying mechanisms remain elusive. An important characteristic feature of S100 proteins is their dual function, inside and outside the cell. In this review, we focus on the intracellular function of S100A4. The review contains structural analysis of S1004 in comparison with other members of S100 proteins. Possible modes of the interaction of S100 proteins with targets are described. Several examples of best-studied molecular interactions involving S100A4 with heavy chain of nonmuscle myosin IIA, LAR-interacting protein liprin beta1 and tumor suppressor protein p53 are provided. We suggest that the binding of S100A4 to these molecules is critical for the S100A4 function. Further studies of the implications of these interactions in different molecular pathways may shed additional light on the role of S100A4 protein in the control of tumor cell motility and migration. We discuss the approaches for down-regulation of S100A4 expression and their potential for application in the clinics.

Exchange Protein Directly Activated by Cyclic AMP Increases Melanoma Cell Migration by a Ca2+-Dependent Mechanism

“…It is known that S100A4, a Ca 2+ binding protein, activates MHCIIA, leading to actin assembly (22)(23)(24)(25) and thus enhanced cell migration through lamellipodia formation (26). We therefore hypothesized that Epac enhances the interaction between S100A4 and MHCIIA, and thus, actin assembly.…”

Unexpected deeds of familiar proteins: Interplay of Hsp70, PGRP S / Tag7, and S100A4 / Mts1 in host vs. cancer combat

“…31 The correlation between the metastatic potential and the Mts1 expression has been a major argument implicating Mts1 in metastasis. [31][32][33][34] Again, it must at once be said that Mts1 is often no less strongly expressed in the host antitumor effectors. 32,35 We have lately shown 13 that the cytotoxic action of Tag7·Hsp70 on largely susceptible tumor-derived cells (L929) is indeed diminished in the presence of excess Mts1, which competitively disrupts the binary complex.…”

Opposite roles of metastasin (S100A4) in two potentially tumoricidal mechanisms involving human lymphocyte protein Tag7 and Hsp70

“…This small (Ϸ10 kDa) readily dimerizing polypeptide can take part in quite diverse processes both inside and outside the cell (2,3). Particularly, it has been implicated in tumor metastasis (1,(4)(5)(6)(7). However, Mts1 may be highly expressed in various cells of the host defense system (4,8), and among them, T lymphocytes, which are essential agents of antitumor defense.…”