A group of researchers appears to have found an explanation for the relative lack of cancer in elephants, whose large size suggests they should have high rates of cancer-causing DNA mutations. In a paper published in Cell Reports, the investigators described the mechanism through which elephants’ genetic systems are able to identify and destroy cells with damaged DNA, thereby preventing cancerous cells from spreading.
Each time a cell replicates, there is a chance that the copy’s DNA will be damaged, resulting in a mutation. Animals with many cells, such as elephants, should therefore have proportionately higher rates of cancer, but the researchers found that elephants develop cancer at a rate similar to or even lower than that of humans.
The team determined that elephants have a gene called p53, which produces a protein that can detect damaged DNA. While humans have just one copy of p53, elephants have 20 copies, resulting in a more robust response to damaged DNA. While investigating this mechanism, the researchers discovered LIF6, a gene unique to elephants. Once activated by p53, the LIF6 gene creates proteins that kill targeted cells, preventing cells with damaged DNA from replicating.
The researchers expressed optimism that the discovery could provide inspiration for new drugs and treatments for humans with cancer. “It might tell us something fundamental about cancer as a process. And if we’re lucky, it might tell us something about how to treat human disease,” said Vincent J. Lynch, PhD, a study coauthor.
Sources: The New York Times, August 14, 2018; Vazquez JM, Sulak M, Chigurupati S, et al. A zombie LIF gene in elephants is upregulated by TP53 to induce apoptosis in response to DNA damage. Cell Reports. 2018;24:1765-76.