Cancer is a friend to no one, but a “zombie gene,” known as LIF6, which still exists in elephants, may be useful in helping end this deadly disease.
LIF6 is a gene that has gone dead in virtually every other animal except for elephants, but researchers have shown that LIF6 is responsible for fighting cancerous mutations in elephants, which rarely get the disease.
In the study, published in Cell Reports, researchers Juan Manuel Vazquez, Michael Sulak, Sravanthi Chigurupati and Vincent J. Lynch show that elephants may be crucial to understanding Peto’s paradox, which states that “there is no correlation between body size and cancer risk across species.”
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“Here, we show that elephants and their extinct relatives (proboscideans) may have resolved Peto’s paradox in part through refunctionalizing a leukemia inhibitory factor pseudogene (LIF6) with pro-apoptotic functions,” the researchers wrote in the study’s summary.
They continued: “These results suggest that refunctionalizing of a pro-apoptotic LIF pseudogene may have been permissive (although not sufficient) for the evolution of large body sizes in proboscideans.”
“Genes duplicate all the time,” said Dr. Lynch, assistant professor of human genetics at the University of Chicago and the study’s senior author, in an interview with the University of Chicago. “Sometimes they make mistakes, producing non-functional versions known as pseudogenes. We often refer to these dismissively as dead genes.”
Lynch and his colleagues were initially studying the p53 gene in elephants, but found that LIF6 (leukemia inhibitory factor 6) effectively evolved to create a new “on” switch, bringing it back from the dead.
“Hence, zombie,” Lynch told the University of Chicago. “This dead gene came back to life. When it gets turned on by damaged DNA, it kills that cell, quickly. This is beneficial, because it acts in response to genetic mistakes, errors made when the DNA is being repaired. Getting rid of that cell can prevent a subsequent cancer.”
Elephants have 20 copies of the p53 gene in their genome, whereas humans only have one. This gene is known as a tumor suppressor, according to a 2015 article in Nature.
Once the LIF6 gene is activated by p53, it kills the afflicted cell fairly quickly, producing a protein that ultimately destroys the cell’s mitochondria, causing the cell to die.
When the LIF6 gene was blocked inside elephants, the diseased cells eventually turned cancerous.
Interestingly enough, when the LIF6 gene was introduced to animals that did not have it activated or lack it, such as mice, they also became cancer-resistant.
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“Elephants get cancer far less than we’d expect based on their size, so we want to understand the genetic basis for this cancer resistance,” Dr. Lynch added in comments obtained by the Daily Mail.
The impact a cancer-killing drug could have on the population would be nothing short of astounding.
According to the National Cancer Institute, it’s estimated that 2018 will see approximately 1.74 million new cases of cancer in the U.S. and 609,640 people will die from the disease.
The NCI adds the most common forms of cancers (in descending order according to estimated new cases) are breast cancer, lung and bronchus cancer, prostate cancer, colon and rectum cancer, while mentioning several others.
“From an evolutionary biology perspective, it’s completely fascinating,” pediatric oncologist Joshua Schiffman told National Geographic.
Scientists now hope that drugs that mimic the effects of the LIF6 gene could lead to new forms of cancer treatments for humans in the not too distant future.
“Maybe we can find ways of developing drugs that mimic the behaviors of the elephant’s LIF6 or of getting cancerous cells to turn on their existing zombie copies of the LIF gene,” Dr. Lynch said.
Follow Chris Ciaccia on Twitter @Chris_Ciaccia