Protein Found to Stimulate Growth of Intestinal Tumours

A team of researchers from the University of Toronto has discovered a protein that supports the growth of many forms of colorectal cancer. Their study, the results of which were published in the scientific journal Journal of Cell Biology, established that a protein called Importin-11 transports the oncogenic protein β-catenin directly into the nuclei of intestinal cancer cells, where it stimulates cell proliferation, meaning their uncontrolled division. The scientists attempted to inactivate this stage of transport, which allowed them to block the growth of most colorectal tumours caused by elevated levels of β-catenin.

Colorectal cancer is among the most commonly occurring cancers, and its incidence has been steadily rising in recent years: nearly 600,000 cases of this disease are diagnosed worldwide each year. The term "colorectal cancer" refers to a whole group of tumours that develop from the cells of the mucous membrane of the lower parts of the intestine, primarily the colon and rectum. Their danger lies in their ability to metastasize quickly, invading surrounding tissues.

The overwhelming majority of intestinal tumours are caused by mutations in the APC gene, which is part of a group of genes that suppress cancer development. These mutations, in particular, stimulate excessive production of the protein β-catenin. High concentrations accumulate in the cell nuclei, where they can activate numerous genes responsible for cell proliferation and contribute to the growth and survival of colorectal tumours. However, until recently, scientists did not have a clear understanding of how this oncogenic protein penetrates the cell nuclei after its levels are elevated.

"The uncertainty of the molecular mechanisms underlying the transport of β-catenin into the nuclei of cells prompted us to determine which genes are necessary to maintain the continuous activity of this protein in intestinal tumour cells that carry mutations in the APC gene," says Stefan Angers, a professor in the Department of Pharmacy at the University of Toronto.

Using advanced CRISPR gene-editing technology, the team developed a new technique that allowed them to scan the entire genome for genes that support the activity of β-catenin in malignant intestinal cells after its concentrations were elevated due to mutations in APC. Of all the genes identified, the scientists focused on IPO11, which encodes a protein called Importin-11, known for its role in transporting various molecules into cell nuclei.

The specialists found that this protein, by binding to β-catenin, escorts it into the nuclei of colorectal cancer cells with mutations in the APC gene. After the researchers removed Importin-11 from these cells, they prevented β-catenin from entering the nuclei and activating its target genes.

At the same time, they found that levels of this protein are often elevated in human intestinal tumour cells. Furthermore, its removal suppressed the growth of tumours formed by cancer cells with the mutant APC gene.

"The results of our study suggest that Importin-11 is necessary for the growth of colorectal tumours," says Professor Angers. A deeper understanding of how this protein transports β-catenin into cell nuclei may help researchers develop new treatment methods that block this process and thereby slow the growth of malignant intestinal formations caused by mutations in the APC gene.