Gene behind third of cancers turned off by scientists

DNA structure on science background. 3d illustration
Deleting a region of the gene meant it was not expressed in laboratory cells. (Stock, Getty Images)

Scientists have turned off a gene that is involved in a third of all cancers in a laboratory experiment.

One in two people born after 1960 in the UK will develop the disease at some point in their life, which can be triggered by genetics or lifestyle habits, like smoking or excessive alcohol consumption.

Nevertheless, the gene GLI1 has been linked with a third of cancer cases by causing the uncontrolled division of cells, tumour "migration" and chemotherapy resistance.

A team from the Lurie Children's Hospital of Chicago found removing a region involved in GLI1's expression turned the gene off in human cells in the laboratory.

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The "promising" results may "prove to be a fruitful treatment strategy for cancer", according to the scientists.

Medical 3D illustration of a dividing cancer cell with a cell surface
One in two people born after 1960 in the UK will statistically develop cancer at some point in their life. (Stock, Getty Images)

"From previous research, we know GLI1 drives the unrelenting cell proliferation that is responsible for many cancers, and this gene also stimulates its own expression,” said study author Dr Philip Iannaccone.

"We established in living human embryonic stem cells 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."

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The Lurie scientists used the gene-editing tool CRISPR to delete the "binding region" of GLI1's DNA in human stem cells derived from embryos.

Stem cells are basic cells that can change into a more specialised form of cell. Embryonic stem cells are taken from three to five-day-old embryos, when they are known as blastocysts and have around 150 cells.

The results – published in the journal Stem Cells – reveal when the binding region was deleted, GLI1 was turned off in the cells.

This then interfered with the gene's normal activity of driving embryonic blood, bone and nerve cell development.

"A surprising aspect of this work was turning GLI1 off affected stem cell differentiation to all three embryonic lineages," said co-author Yekaterina Galat.

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Turning off GLI1's binding region is not thought to have any negative consequences, however.

"The developmental function of GLI1 ends after birth, so if we manage to stop its expression in the context of cancer, it should not have negative consequences to normal biology," said Dr Iannaccone.

The scientists stressed further research is required.

"Our team plans to study GLI1 associated proteins that assist in regulation of GLI1 expression through its binding region," said Dr Iannaccone.

"Targeting these proteins as a means to stop GLI1 activity could prove to be a fruitful treatment strategy for cancer."

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