Toronto: Researchers have found a new drug for the treatment of colorectal cancer, in the form of a key protein that supports the growth of many types of bowel cancers.
The study, published in the ‘Journal of Cell Biology’, shows that a protein called ‘Importin-11’ transports the cancer-causing protein ‘betacatenin’ into the nucleus of colon cancer cells, where it can drive cell proliferation.
Inhibiting this transport step could block the growth of most colorectal cancers caused by elevated ‘betacatenin levels’, according to the researchers at the University of Toronto in Canada.
Around 80 per cent of colorectal cancers are associated with mutations in a gene called APC that result in elevated levels of the ‘betacatenin’ protein.
This increase in betacatenin is followed by the protein’s accumulation in the cell nucleus, where it can activate numerous genes that drive cell proliferation and promote the growth and maintenance of colorectal tumours.
“Because the molecular mechanisms underlying betacatenin nuclear transport remains unclear, we set out to identify genes required for continuous betacatenin activity in colorectal cancer cells harbouring APC mutations,” said Stephane Angers, a professor at the University of Toronto.
Using CRISPR DNA editing technology, Angers and colleagues, including graduate student Monika Mis, developed a new technique that allowed them to screen the human genome for genes that support betacatenin’s activity in colorectal cancer cells after its levels have been elevated by mutations in APC.
One of the main genes they identified was ‘IPO11’, which encodes a protein called Importin-11 that is known to be involved in nuclear import.
The researchers found that Importin-11 binds to betacatenin and escorts it into the nucleus of colorectal cancer cells with mutations in APC. Removing Importin-11 from these cells prevented betacatenin from entering the nucleus and activating its target genes.
“We conclude that Importin-11 is required for the growth of colorectal cancer cells,” Angers said.
Agencies