The oncogenic functions of mutant p53 proteins

p53 is the most frequently mutated gene in most cancers. Mutations can lead to loss of p53 expression or mutant p53 expression. Mutant p53 proteins are often impaired for wild type functions and have been shown to dominant negatively regulate any remaining wild type p53. Interestingly, p53 mutants in mice and cells have been shown to do more and act like an oncogene in driving metastasis and promoting chemoresistance. Previously, we have investigated the molecular mechanisms underlying this oncogenic behaviour and have shown that mutant p53 promotes invasion and metastasis by enhancing RCP dependent recycling of integrins and growth factor receptors from intracellular vesicles to the plasma membrane. Novel data in the lab now show that other molecules including the multi-drug transporter p-glycoprotein are also regulated by mutant p53 in an RCP-dependent manner and thereby convey chemoresistance. In addition, we have encountered a novel phenomenon of mutant p53 in promoting cancer cell engulfment. We can see this in cells and in patients samples and have demonstrated this to be important for tumour growth in xenografts and are currently determining the consequences and the molecular mechanisms underlying this behaviour. A better understanding of mutant p53 function will be pivotal to help in designing strategies to use p53 status in the clinic for therapeutic purposes.