Mutually antagonistic actions of S100A4 and S100A1 on normal and metastatic phenotypes

Abstract

Increased levels of the homodimeric calcium-binding protein, S100A4, have been shown to cause a metastatic phenotype in at least three independent model systems of breast cancer and its presence in carcinoma cells has been shown to be associated with a reduction in the survival of patients suffering from a range of different cancers. S100A4 has been shown to interact in vitro with another member of the S100 family of proteins, S100A1. The purpose of the present study was to find out whether S100A1 could affect S100A4 function. Fluorescence resonance energy transfer was used to show the interaction of S100A4 and S100A1 in living cells and the binding affinities between S100A4 and S100A1 were determined using a biosensor. S100A1 reduced the S100A4 inhibition of nonmuscle myosin A self-association and phosphorylation in vitro. S100A1 reduced S100A4 induced motility and growth in soft agar and metastasis in vivo. The results show for the first time that interactions between different S100 proteins can affect cancer-related activity, and that the presence of S100A1 protein in carcinoma cells might modulate the effect of S100A4 on their metastatic abilities.

Dynamic assembly properties of nonmuscle myosin II isoforms revealed by combination of fluorescence correlation spectroscopy and fluorescence cross-correlation spectroscopy

“…FRET experiments demonstrated the direct association of a C-terminal rod fragment of the myosin IIA heavy chain with Mts1 in living cells (46). It was also suggested that this interaction with myosin IIA is important for Mts1's ability to induce the metastatic phenotype (47,48). These observations strongly imply that the interaction of myosin IIA with Mts1 in the leading edge of migrating cell would be essential for metastasis.…”

The metastasis associated protein S100A4: role in tumour progression and metastasis

“…S100A4 can form heterodimers with S100A1 in vitro (Tarabykina et al, 2000;Wang et al, 2000). Significantly it was shown that the interaction between these two proteins, reduces motility and metastatic ability of S100A4 transformed cells (Wang et al, 2005).…”

S100A4 (Mts1) gene overexpression is associated with invasion and metastasis of papillary thyroid carcinoma

“…Flatmark et al (2003) has demonstrated that S100A4 nuclear localisation correlated with tumour stage and aggressiveness of colorectal carcinoma. A recent study has shown that A100A1, another member of the S100 family of proteins, can interact with S100A4 to modulate the effect of S100A4 on their metastatic abilities (Wang et al, 2005).…”