New cells going awry as they replace older cells in the body can often lead to cancer, but a study in the Cell Reports journal describes a way that elephants may lead scientists to new ways to combat human cancers.
Bigger may be better
Since cells are a critical component of acquiring cancer, it is reasonable to think that a large mammal, such as an elephant, would develop more cancers than a smaller mammal, such as a human, since it would clearly have hundreds of times more cells in its large body. However, elephants rarely get cancer in any form.
A paper published by Joshua Schiffman, a pediatric oncologist at the University of Utah, and his team, pointed out an interesting finding showing organism size and cancer rates are the reverse of what rational thought would suppose. In our bodies is a tumor-suppressing gene – P53. Whereas humans have one copy of this important gene; elephants have 20.
The purpose of P53
P53 acts as a genetic triage manager, recognizing abnormal DNA and determining whether to repair or destroy the cell. This is where elephants excel with their overload of P53. For the most part, damaged cells in elephants are killed, not repaired, while other mammals – including humans – tend to try to repair first. Since these damaged cells are killed immediately in elephants, they don’t have time to become cancerous.
Vincent Lynch, who led the study team and is an evolutionary biologist at the University of Chicago, stated, “Elephants are weird. Their cells just die if you give them DNA damage.” He wanted to know why. This quest lead to finding the answer in LIF genes.
What are LIF genes?
He found this strange phenomenon by looking for what genes might be genetically different between an elephant and other small-bodied mammals. Primarily they were looking for genes with extra copies. That’s when he found that one gene, Leukemia Inhibitory Factor, or LIF – known for enhancing fertility – also killed aberrant cells. Almost every mammal, including humans have one copy of LIF, but elephants, manatees, and the hyrax, have many. Elephants have anywhere from 7 to 11 copies. LIF6 is the only gene that appears to act as the executioner when P53 orders a cell killed and only elephants have that specific gene.
Lynch and his team confirmed their suspicions by damaging DNA from African elephant cells in the lab. This pulled the trigger for P53 to give orders to the LIF6 gene, which then killed the damaged cells. But, when LIF6 was made non-functioning, the P53 had nowhere to turn and the elephant sensitivity to cell damage no longer worked, leaving the damaged cells free to roam and multiply.
Ways to combat human cancers are just beginning
P53 and LIF6 functions in elephants are remarkable finds, but there is more to study. In fact, one ongoing study focuses on a set of genes that works to repair elephant DNA instead of killing the cells.
Researchers hope that these in-depth studies of cancer defenses in elephants will be the start of finding additional treatments for cancer in humans.