Ancient viruses can reactivate and fuel cancer development 

Researchers at the University of Colorado Boulder have made a significant discovery about endogenous retroviruses, ancient viral DNA embedded in the human genome, which can influence the development and survival of cancer. 

These viral remnants, previously considered “junk” DNA, can reactivate and play a crucial role in cancer biology. 

The study, published in the journal Science Advances, reveals that silencing these retroviruses can enhance the effectiveness of cancer treatments.

Retroviruses can act as genetic switches 

According to Edward Chuong, the study’s senior author and assistant professor at CU Boulder’s BioFrontiers Institute, endogenous retroviruses make up about 8% of the human genome. 

These retroviruses infiltrated the cells of our evolutionary ancestors, embedding their genetic material into sperm, eggs, and embryos, thereby integrating into the genome over generations. 

Despite losing the ability to produce functional viruses, these sequences can act as genetic switches, influencing nearby genes.

Beneficial and harmful roles of retroviruses 

Chuong’s research highlights both the beneficial and harmful roles of these retroviruses. 

While some have been domesticated for evolutionary benefits, such as the development of the placenta and immune responses, others can be detrimental, particularly in the context of cancer. 

High activity in several cancers

To explore their impact on cancer, Chuong and first author Atma Ivancevic analyzed genomic data from 21 human cancer types. 

The experts found that a lineage of endogenous retroviruses, specifically LTR10, showed high activity in several cancers, including lung and colon cancer. Further analysis revealed that LTR10 was active in about a third of colorectal cancer patients.

Using the CRISPR gene editing tool, the team silenced LTR10 sequences in cancer cells, resulting in the deactivation of critical genes that promote cancer development. 

This finding was supported by experiments in mice, where removing the LTR10 switch from tumor cells improved the effectiveness of treatments aimed at shrinking tumors.

Disrupting a critical cellular pathway 

One key discovery was that LTR10 influences the MAP-kinase pathway, a critical cellular pathway involved in many cancers. 

The study suggests that existing MAP-kinase inhibitors may work partly by disabling the LTR10 switch, which regulates around 70 cancer-associated genes in this pathway.

Chuong and his team propose that as people age, their genomic defenses weaken, allowing these ancient viruses to reawaken and contribute to various health problems. 

“The origins of how diseases manifest themselves in the cell have always been a mystery,” Chuong said. “Endogenous retroviruses are not the whole story, but they could be a big part of it.”

Retroviruses and cancer biology 

The research underscores the importance of understanding the role of endogenous retroviruses in modern diseases. 

By shedding light on how these ancient viral sequences can be reactivated and influence cancer biology, the study opens up new avenues for improving cancer treatment and potentially addressing other health issues linked to these viral remnants.

Part human, part virus

Studies show about 8% of the human genome is made up of endogenous retroviruses that slipped into the cells of our evolutionary ancestors, coaxing their hosts to copy and carry their genetic material. 

Over time, they infiltrated sperm, eggs and embryos, baking their DNA like a fossil record into generations to come – and shaping evolution along the way.

“Part human, part virus” is a way to describe these sequences. Even though they can no longer produce functional viruses, Chuong’s own research has shown that endogenous retroviruses can act as “switches” that turn on nearby genes. 

Some have contributed to the development of the placenta, a critical milestone in human evolution, as well as our immune response to modern-day viruses like COVID.

“There’s been a lot of work showing these endogenous retroviruses can be domesticated for our benefit, but not a lot showing how they might hurt us,” he said.

Gene expression and cancer development 

Chuong’s findings reveal that these sequences, when activated, can influence the expression of genes that promote cancer development. This discovery is crucial as it suggests that targeting these sequences could improve cancer treatment outcomes. 

In particular, the research showed that silencing LTR10 sequences led to the deactivation of cancer-promoting genes, enhancing the effectiveness of existing cancer therapies.

The research also highlights the role of the MAP-kinase pathway, a cellular pathway frequently altered in cancers. 

The study suggests that existing MAP-kinase inhibitors may work by disabling the LTR10 switch, which regulates numerous cancer-associated genes within this pathway.

Significance of the study

This research opens new avenues for understanding the role of endogenous retroviruses in modern diseases and improving cancer treatments by targeting these ancient viral sequences. 

By illuminating how these viral remnants influence cancer biology, the study paves the way for more effective therapies and a better understanding of disease mechanisms.

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