Cancer: A Protein Aggregation Disease

Aggregated proteins, the longtime hallmarks of neurodegenerative disorders such as Alzheimer’s disease, also play a role in cancer, new research suggests. Preventing aggregation of proteins, such as the tumor suppressor protein p53, could thus become a strategy for anticancer drug development. A team led by Joost Schymkowitz and Frederic Rousseau at Catholic University, in Leuven, Belgium, took a look at p53, which binds DNA to help regulate cell cycles. It’s also mutated in 50% of all cancers, and about one-third of p53 mutations cause the protein to misfold. The Leuven team found that these misfolding mutations lead to aggregation of both diseased and wild-type p53, as well as aggregation of two other regulatory proteins, p63 and p73 (Nat. Chem. Biol., DOI: 10.1038/nchembio.546). “Overall, our study reveals a novel disease mechanism for mutant p53,” the researchers note, “and suggests that, at least in some respects, cancer could be considered an aggregation-associated disease.” The notable difference between aggregation of proteins in cancer cells and those in neurodegeneration is that aggregation in cancer leads to uncontrolled cell growth, whereas in neurodegeneration it leads to cell death.