Personalized & Precision Medicine: March 2021

Scientists find gene that could ‘stop one-third of all cancers from developing’

Chris Melore

March 2, 2021, CHICAGO, Ill. (StudyFinds.org) — Cancer can come in many forms and each one has a different, devastating impact on the body. On a genetic level however, many of these cancers are the same. A new study finds targeting one specific gene may stop one-third of all cancers from developing. Researchers in Chicago say they’re targeting the GLI1 gene, which is instrumental in helping cancer to spread throughout the body.

A team from the Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital of Chicago finds turning off the GLI1 gene can keep cells from multiplying out of control. This is one of the main characteristics in cancer growth.

“From previous research, we know that GLI1 drives the unrelenting cell proliferation that is responsible for many cancers, and that this gene also stimulates its own expression,” says co-senior author Philip Iannaccone, MD, PhD, in a media release. “We established in living human embryonic stem cells that removing the GLI1 regulatory region eliminated GLI1 expression and halted its activity. These findings are promising and could point to a therapeutic target for cancer.”

Editing cancer out of the human genome

Dr. Iannaccone and his team used CRISPR gene editing technology to remove the binding region from GLI1 genes in human embryonic stem cell DNA. Without this specific region, the study finds GLI1 stays dormant. Doing so interferes with the gene’s normal ability to drive the development of blood, bone, and nerve cells.

“A surprising aspect of this work was that turning GLI1 off affected stem cell differentiation to all three embryonic lineages,” explains first author Yekaterina Galat, BS, a research associate at the Manne Research Institute at Lurie Children’s.

Study authors note that the usefulness of GLI1 ends after birth, when the fetus is done turning stem cells into the various components of the body. Their activation after that point can lead to the abnormal cell division and tumor growth which destroys healthy tissue.

“If we manage to stop its expression in the context of cancer, it should not have negative consequences to normal biology,” Dr. Iannaccone adds.

The team says GLI1 has a connection to about one in three human cancers. Along with making cells multiply, active GLI1 genes can also increase tumor cell migration and makes the disease more resistant to chemotherapy.

“Our team plans to study GLI1 associated proteins that assist in regulation of GLI1 expression through its binding region,” Dr. Iannaccone concludes. “Targeting these proteins as a means to stop GLI1 activity could prove to be a fruitful treatment strategy for cancer.”

The study appears in the journal Stem Cells.

 

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