Role of Reactivating Mutant p53 Protein in Suppressing Growth and Metastasis of Triple-Negative Breast Cancer

Abstract

Tumor suppressor p53 protein (p53) plays a vital role throughout the body to conserve DNA stability and prevent cancer. Normally, wild-type p53 protein (wtp53) is either degraded or bound to a negative regulator and is inactive. When damage to DNA occurs within a cell, p53 protein is induced and causes cell cycle arrest. This gives cells a chance to repair, but if damage is too severe, cells undergo apoptosis and are rejected. Mutations in the p53 gene (mtp53) are associated with a variety of cancers and occur in 70– 80% of cases of triple-negative breast cancer (TNBC). Importantly, many mutations occur in the DNA binding domain of p53 gene and the altered mutant p53 protein (mtp53) is subsequently not degraded. High levels of mtp53 protein accumulate within the cell, leading to the development of tumors. Therefore, converting mtp53 protein back into its functional wild-type conformation is a promising means by which to prevent or reverse tumor development. Herein we will briefly examine how tumor suppressor wtp53 exerts its effects, the mechanisms involved in protecting cells that undergo DNA damage and ways in which wtp53 prevents tumorigenesis. Using TNBC as an example, we will describe the use of specific compounds to reactivate mtp53 protein function by reconfiguring its structure and outline the potential benefits of mtp53 protein reactivation. We will also briefly discuss current clinical trials aimed at reactivating mtp53 protein in order to cure certain cancers. Finally, we make the recommendation that greater emphasis should be placed on testing naturally occurring compounds that are generally non-toxic to re-activate mtp53 protein and control progression of TNBC.