Researchers Discover Gene Family That Converts Cancer Cells Into Aggressively Growing Stem Cells

Examining 130 studies on gene expression in 10 cancers has revealed that the overexpression of four related genes results in worse outcomes for patients, including reduced survival rates.

In a study published in the journal Oncotarget, researchers from the Georgetown Lombardi Comprehensive Cancer Center showed that the Ly6 gene family lets cancer cells act like stem cells, dividing and growing continuously.

According to senior investigator Geeta Upadhyay, Ph.D., they believe that the Ly6 family of genes leads to cancers that easily metastasize, are resistant to drugs and highly difficult to destroy.

Currently, the researchers are working on novel agents designed to inhibit the expression of Ly6 genes. Their work builds upon the results of Upadhyay's own study on Sca1, a mouse gene used for checking for cancer stem cells in animals.

Back in 2011, she discovered that Sca1 was not just a biomarker but also had a crucial role in producing and maintaining stem-like qualities in cancer stem cells.

When Upadhyay checked to see how the mouse gene would work in humans, she saw that the Ly6 gene family were mapped on the same chromosome locations that corresponds to Sca1's spots in the mouse genome. The gene family and the mouse gene were also similar in structures.

To determine if the Ly6 gene family is an important factor in cancer in humans, the researchers analyzed 130 studies about patient genes and cancer outcomes. They found that some Ly6 gene members are not active within normal tissues, but are expressed in prostate, pancreatic, neck and head, lung, ovarian, cervical, colorectal, brain and central nervous system and bladder cancers.

And when the genes from the Ly6 family were overexpressed, patient outcomes were poor, with survival rates reduced in those with brain and central nervous system, bladder, lung, gastric, colorectal and ovarian cancers.

"Correlation between Ly6 gene expression and poor patient survival in multiple cancer types indicate that this family of genes will be important in clinical practice – not only as a marker of poor prognosis, but as targets for new drugs," said Upadhyay.

The study received funding support from an American Cancer Society Institutional Research Grant and the National Cancer Institute. It is also a perfect example of what happens when researchers share data, supporting the "cancer moonshot" proposal announced at President Barack Obama's State of the Union address to hasten research.

Photo: National Institutes of Health | Flickr

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