Metastasis-Inducing Mts1/S100A4 Protein Binds to Tumor Suppressor p53 Protein

Abstract

This study for the first time demonstrates a physical and functional interaction between the Ca2+-binding protein Mts1/S100A4 and tumor suppressor p53 protein. Using different in vitro and in vivo approaches, we have found that Mts1 can bind to the C-terminal regulatory domain of p53. The Mts1 binding to p53 promotes activation of the reporter gene transcription in vivo. A modulation of the p53 target gene (p21/WAF,bax,mdm-2, and thrombospondin-1) expression was observed upon Mts1 induction in the cells expressing the wild-type p53. These results suggest that the ability of Mts1 to enhance p53-dependent apoptosis of tumor cells leads to the decrease/disappearance of the tumor cells expressing the wild-type p53. Thus, Mts1 promotes selection of more aggressive, metastatic phenotype during tumor progression.