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Scientists at the Stanley Manne Children’s Research Institute at the Ann & Robert H. Lurie Children’s Hospital in Chicago found that a region within the DNA of the cancer-promoting GLI1 gene is directly responsible for regulating the expression of this gene. These results, published in the journal Stem Cells, suggest that this region within GLI1 could potentially be used as a cancer treatment, since turning off GLI1 would disrupt the excessive cell division characteristic of cancer.

“We know from previous research that GLI1 drives the relentless cell proliferation that is responsible for many cancers, and that this gene also stimulates its own expression,” says co-senior author Philip Iannaccone, MD, Ph.D., professor Emeritus at the Manne Research Institute at the Feinberg School of Medicine at Lurie Children’s and Northwestern University. “We found in living human embryonic stem cells that removal of the GLI1 regulatory region eliminated GLI1 expression and stopped its activity. These results are promising and could indicate a therapeutic target for cancer.”

Dr. Iannaccone and colleagues used CRISPR gene editing technology to delete the binding region of GLI1 DNA in human embryonic stem cells. They found that without this region, GLI1 remained switched off, which interfered with the gene’s normal activity to drive embryonic development of blood, bones, and nerve cells.

“A surprising aspect of this work was that turning off GLI1 impaired the differentiation of stem cells in all three embryonic lineages,” says lead author Yekaterina Galat, BS, research fellow at the Manne Research Institute at Lurie Children’s.

“The developmental function of GLI1 ends after birth, so if we can stop its cancer-related expression, it shouldn’t have any negative effects on normal biology,” explains Dr. Iannaccone.

GLI1 expression is associated with about a third of all cancers in humans. In addition to promoting cell proliferation, GLI1 expression increases tumor cell migration and is associated with resistance to chemotherapeutic agents.

“Our team plans to investigate GLI1-associated proteins that support the regulation of GLI1 expression through their binding region,” says Dr. Iannaccone. “Targeting these proteins as a means of terminating GLI1 activity could prove to be a fruitful treatment strategy for cancer.”

Stem cell therapy corrects skull and brain function in the mouse model of childhood disorder

More information:
Yekaterina Galat et al., CRISPR processing of the first GLI1 intron abolishes GLI1 expression and changes the binding of stem cells, stem cells, differently

First published: January 26, 2021 doi.org/10.1002/stem.3341 Provided by Ann & Robert H. Lurie Children’s Hospital, Chicago

Quote: Potential target for the treatment of many cancers in the GLI1 gene (2021, March 1), accessed March 1, 2021 from https://medicalxpress.com/news/2021-03-potential-cancers-gli1-gene.html

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