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Two key events that turn normal cells into cancer

University of Pennsylvania News Nov 18, 2020

More than 100 different cancers can arise all over the body, but two universal metabolic pathways may tie them all together, researchers from the Perelman School of Medicine report in a new study published online in Cell Metabolism. Researchers have long believed all cancers are governed by a common set of fundamental processes. Exactly what those were, however, has remained elusive.

The findings may inform the development of new therapies that could treat any tumor type. Having a unifying mechanism could inform new therapeutic approaches to prevent normal cells from transforming into any type of tumor, be it breast, prostate, or colon, for example.

The team discovered how the transformation from a phenotypically normal cell to a cancerous one involves the enhancement of two key elements: antioxidant defense and nucleotide synthesis. Genes associated with cancer, they found, are super charging some cells to fight off oxidative stress and synthesize nucleotides, which cells need to survive and rapidly grow, respectively.

“Since the early 1980s, numerous cancer genes have been identified. However, they often affect multiple cellular processes, which makes it very hard to really summarize what exactly turns cells cancerous,” says senior author Xiaolu Yang, a professor of cancer biology in the Perelman School of Medicine. “We took a unique approach and looked at the cellular changes driven by a particular metabolic enzyme, which turned out to be the key here. Strikingly, we found that for a phenotypically normal cell to become a cancer cell, all it needs to do is to be equipped with the extra capacity to endure oxidative stress and produce nucleotides.”

Shut down these metabolic pathways, the study suggests, and the cells don’t become cancerous.

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