p53 amyloid formation induced cellular transformation and tumor formation in xenograft model

p53 mutation and its subsequent loss of function along with gain of oncogenic functions is associated with cancer. However, the exact mechanism of how altered p53 acts as an oncogene is not clear yet. Recently, it was suggested that p53 aggregation and amyloid formation leads to both loss of tumor suppressive function and gain of oncogenic functions in cells. In this study, we directly demonstrate that wild-type p53 amyloid formation imparts oncogenic properties to normal cells. Cells with p53 amyloid aggregates show enhanced survival, apoptotic resistance with increased proliferation and migration rate. We further establish the tumorigenic potential of p53 amyloid containing cells in a mice xenograft model. Furthermore, these tumors tested positive for p53 amyloid aggregates. Comprehensive gene-expression analysis suggests that p53 amyloid formation triggers aberrant expression of pro-oncogenes while downregulating the tumor suppressor associated genes. Interestingly, disaggregating p53 rescues the cellular transformation and also inhibits tumor development in mice. We propose that wild-type p53 amyloid formation can potentially contribute to initiation of tumor development. MCF10A cells were cultured in DMEM growth medium under appropriate conditions, treated with 30 µM of p53 core fibrils and were incubated for 48 hours at 37 °C in a 5 % CO2 incubator.