S100A4 is a small calcium-binding protein that is commonly overexpressed in a 
range of different tumor types, and it is widely accepted that S100A4 has an 
important role in the process of cancer metastasis. In vitro binding assays has 
shown that S100A4 interacts with the tumor suppressor protein p53, indicating 
that S100A4 may have additional roles in tumor development. In the present 
study, we show that endogenous S100A4 and p53 interact in complex samples, and 
that the interaction increases after inhibition of MDM2-dependent p53 
degradation using Nutlin-3A. Further, using proximity ligation assay, we show 
that the interaction takes place in the cell nucleus. S100A4 knockdown 
experiments in two p53 wild-type cell lines, A549 and HeLa, resulted in 
stabilization of p53 protein, indicating that S100A4 is promoting p53 
degradation. Finally, we demonstrate that S100A4 knockdown leads to 
p53-dependent cell cycle arrest and increased cisplatin-induced apoptosis. Thus, 
our data add a new layer to the oncogenic properties of S100A4 through its 
inhibition of p53-dependent processes.