An enzyme that defends human cells against viruses can help drive cancer evolution towards greater malignancy by causing myriad mutations in cancer cells, according to a study led by investigators at Weill Cornell Medicine. The finding suggests that the enzyme may be a potential target for future cancer treatments.
In the new study, published recently in the journal Cancer Research, scientists used a preclinical model of bladder cancer to investigate the role of the enzyme called APOBEC3G in promoting the disease and found that it significantly increased the number of mutations in tumor cells, boosting the genetic diversity of bladder tumors and hastening mortality.
“Our findings suggest that APOBEC3G is a big contributor to bladder cancer evolution and should be considered as a target for future treatment strategies,” said study senior author Dr. Bishoy M. Faltas, assistant professor of medicine in the Division of Hematology and Medical Oncology and of cell and developmental biology at Weill Cornell Medicine, and an oncologist who specializes in urothelial cancers at NewYork-Presbyterian/Weill Cornell Medical Center.
The inherent hazardousness of these enzymes suggests that mechanisms must be in place to prevent them from harming cellular DNA. However, starting about a decade ago, researchers using new DNA-sequencing techniques began to find extensive APOBEC3-type mutations in cellular DNA in the context of cancer. In a 2016 study of human bladder tumor samples, Dr. Faltas, who is also director of bladder cancer research at the Englander Institute for Precision Medicine and a member of the Sandra and Edward Meyer Cancer Center, found that a high proportion of the mutations in these tumors were APOBEC3-related—and that these mutations appeared to have a role in helping tumors evade the effects of chemotherapy.
Such findings point to the possibility that cancers generally harness APOBEC3s to mutate their genomes. This could help them not only acquire all the mutations needed for cancerous growth but also boost their ability to diversify and “evolve” thereafter—enabling further growth and spread despite immune defenses, drug treatments, and other adverse factors.
In the new study, Dr. Faltas and his team, including first author Dr. Weisi Liu, a postdoctoral research associate, addressed the specific role of APOBEC3G in bladder cancer with direct cause-and-effect experiments.
APOBEC3G is a human enzyme not found in mice, so the team knocked out the gene for the sole APOBEC3-type enzyme in mice, replacing it with the gene for human APOBEC3G. The researchers observed that when these APOBEC3G mice were exposed to a bladder cancer-promoting chemical that mimics the carcinogens in cigarette smoke, they became much more likely to develop this form of cancer (76% developed cancer) compared with mice whose APOBEC gene was knocked out and not replaced (53% developed cancer). Moreover, during a 30-week observation period, all the knockout-only mice survived, whereas nearly a third of the APOBEC3G mice succumbed to cancer.
To their surprise, the researchers found that APOBEC3G in the mouse cells was present in the nucleus, where cellular DNA is kept using an ‘optical sectioning’ microscopy technique. Previously, this protein had been thought to reside only outside the nucleus. They also found that the bladder tumors of the APOBEC3G mice had about twice the number of mutations compared to the tumors in knockout-only mice.
Identifying the specific mutational signature of APOBEC3G and mapping it in the tumor genomes, the team found ample evidence that the enzyme had caused a greater mutational burden and genomic diversity in the tumors, likely accounting for the greater malignancy and mortality in the APOBEC3G mice. “We saw a distinct mutational signature caused by APOBEC3G in these tumors that is different from signatures caused by other members of the APOBEC3 family,” said Dr. Liu.
Lastly, the researchers looked for APOBEC3G’s mutational signature in a widely used human tumor DNA database, The Cancer Genome Atlas, and found that these mutations appear to be common in bladder cancers and are linked to worse outcomes.
“These findings will inform future efforts to restrict or steer tumor evolution by targeting APOBEC3 enzymes with drugs,” said Dr. Faltas.

News
Silver nanoparticles show promise in fighting antibiotic-resistant bacteria
In a new study, scientists with the University of Florida have found that a combination of silver nanoparticles and antibiotics is effective against antibiotic-resistant bacteria. The researchers hope to turn this discovery into viable [...]
Combating severe cancer with a new drug delivery system
Peritoneal cancer is difficult to treat and has a poor survival prognosis. But a new and effective nanomedicine delivery system is offering some hope. The company is called NaDeNo and is well underway with [...]
New Research Shows How Ketamine Acts As “Switch” in the Brain
According to a new study by researchers at Penn Medicine, ketamine, which is well-known as an anesthetic and is becoming increasingly popular as an antidepressant, dramatically reorganizes activity in the brain, almost as if [...]
Supercharged T Cells: A New Way To Kill Pancreatic Cancer With Minimal Side Effects
A new immunotherapy releases cancer-killing cytokines only within the tumor. Researchers at the University of California San Francisco (UCSF) have developed a new T cell-based immunotherapy that selectively targets cancer cells, producing a powerful anti-cancer cytokine [...]
AI has designed bacteria-killing proteins from scratch – and they work
An AI was tasked with creating proteins with anti-microbial properties. Researchers then created a subset of the proteins and found some did the job. An AI has designed anti-microbial proteins that were then tested [...]
Using nanoparticles, researchers can identify and deliver synergistic combinations of cancer drugs
Treating cancer with combinations of drugs can be more effective than using a single drug. However, figuring out the optimal combination of drugs, and making sure that all of the drugs reach the right [...]
Humanity May Reach Singularity Within Just 7 Years, Trend Shows
By one unique metric, we could approach technological singularity by the end of this decade, if not sooner. A translation company developed a metric, Time to Edit (TTE), to calculate the time it takes for professional [...]
HYPER (Highly Interactive Particle Relics) – A New Model for Dark Matter
Phase transition in early universe changes strength of interaction between dark and normal matter. Dark matter remains one of the greatest mysteries of modern physics. It is clear that it must exist, because without [...]
New Nanoparticles Deliver Therapy Brain-Wide and Edit Alzheimer’s Gene
Summary: Researchers have developed a new family of nano-scale capsules capable of carrying CRISPR gene editing tools to different organs of the body before harmlessly dissolving. The capsules were able to enter the brains of [...]
Cancer’s Secret Weapon? Enzyme That Protects Against Viruses May Fuel Tumor Evolution
An enzyme that defends human cells against viruses can help drive cancer evolution towards greater malignancy by causing myriad mutations in cancer cells, according to a study led by investigators at Weill Cornell Medicine. The [...]
Scientists Uncover Japanese Fruit Juice That May Help Prevent Lung Cancer
Using a mouse model, Japanese researchers unleash the likely mechanism of action of Actinidia arguta (sarunashi) juice on lung cancer development. Lung cancer is a leading cause of death in Japan and across the [...]
In-place manufacturing method improves gas sensor capabilities, production time
When used as wearable medical devices, stretchy, flexible gas sensors can identify health conditions or issues by detecting oxygen or carbon dioxide levels in the breath or sweat. They also are useful for monitoring [...]
In the core of the cell: New insights into the utilization of nanotechnology-based drugs
Novel drugs, such as vaccines against covid-19, among others, are based on drug transport using nanoparticles. Whether this drug transport is negatively influenced by an accumulation of blood proteins on the nanoparticle’s surface was [...]
The costly lesson from COVID: why elimination should be the default global strategy for future pandemics
Imagine it is 2030. Doctors in a regional hospital in country X note an expanding cluster of individuals with severe respiratory disease. Rapid whole-genome sequencing identifies the disease-causing agent as a novel coronavirus. Epidemiological [...]
How Artificial Intelligence Found the Words To Kill Cancer Cells
A predictive model has been developed that enables researchers to encode instructions for cells to execute. Scientists at the University of California, San Francisco (UCSF) and IBM Research have created a virtual library of thousands of “command sentences” [...]
Next-generation, light-activated nanotech for antibiotic-resistant superbugs
It's "lights out" for antibiotic-resistant superbugs as next-generation light-activated nanotech proves it can eradicate some of the most notorious and potentially deadly bacteria in the world. Developed by the University of South Australia and [...]