Scientists Discover Ancient Anti-Cancer Mechanism: DISE

Artistic Rendering of Cancer Cells

A new study reveals an ancient anti-cancer mechanism, DISE, emphasizing the evolutionary role of RNA interference in combating cancer.

A groundbreaking study, recently published in the journal Oncotarget delves into the depths of the cellular world, unveiling a potential ancient anti-cancer mechanism. The research was led by scientists Monal Patel and Marcus E. Peter from Northwestern University.

Despite significant advancements in cancer therapy, cancer still ranks among the leading causes of death worldwide. This systemic ailment, which can affect individuals regardless of age, begins at the cellular level. Single cells, once they acquire mutations, undergo a transformation known as neo-plastic transformation.

Evolutionary Perspective on Cancer

Cell division is the biggest risk factor for the accumulation of mutations, explaining why all multicellular organisms which evolved about 2 billion years ago, are prone to cancer. Given the recent achievements in cancer treatment with immune checkpoint blockade therapies, multicellular organisms may have developed the immune system as a mechanism to eradicate cancerous cells.

“However, the immune system arose relatively recently, ~500 million years ago.”

Moreover, studies have shown that cancer cells can become resistant to the anticancer activity of both the innate and the adaptive immune system. Therefore, while the immune system is important, it is likely not the most vital machinery that emerged in multicellular organisms to prevent cancer formation. The researchers believe that there are other more effective and archaic anti-cancer mechanisms that are conserved during evolution.

The Role of RNA Interference

Of note, RNA interference (RNAi) is a highly conserved biological mechanism for silencing gene expression. While RNAi likely emerged as a defense tool against viruses and other foreign nucleic acids, it has also evolved to have other activities in the cells. The team’s research has identified a new evolutionarily conserved RNAi-based form of cell death that targets essential survival genes: Death Induced by Survival gene Elimination (DISE).

“DISE was discovered through our work on CD95 and its ligand, CD95L, where we found that more than 80% of 26 different short interfering RNAs (siRNAs) and short hairpin RNAs (shRNAs) derived from the two genes, killed multiple cancer cell lines via simultaneous activation of multiple cell death pathways; and we were unable to find a way to inhibit this form of cell death.”

Reference: “DISE, an ancient anti-cancer mechanism that senses mutational load in cancerous cells? ” by Monal Patel and Marcus E. Peter, 25 September 2023, Oncotarget.
DOI: 10.18632/oncotarget.28466

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