H179R and H179Y TP53 mutations promote invasion

We used TCGA and MSK-IMPACT32 datasets to identify that cancers with H179 TP53 mutations are associated with poor patient outcomes. Using models of lung, ovarian, and prostate cancer cells, we show that p53H179R/Y mutants lose canonical p53 function and metabolically reprogram cells by increasing lipid levels via de novo synthesis and/or fatty acid uptake or both, along with an increase in lipid droplets and expression of apolipoprotein E (APOE), and vimentin (VIM). This metabolic reprogramming drives a more invasive phenotype, with mutant cells exhibiting greater invasiveness in 3D collagen matrices compared to TP53-null cells.