p53 amyloid formation is predicted to be involved in cancer initiation, but the direct evidence of how altered p53 acts as an oncogene is lacking. Cells with p53 amyloids show enhanced survival, apoptotic resistance with increased proliferation and migration rates. Proteomic profiling of cells containing p53 aggregates suggests that p53 amyloid formation triggers aberrant expression of pro-oncogenes while downregulating the tumor-suppressive genes. We propose that wild-type p53 amyloid formation can potentially contribute to the initiation of tumor development.