Toronto: Researchers have identified a key protein that supports the growth of many bowel cancers, paving the way for development of new therapies to combat the deadly disease.
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The study, published in the Journal of Cell Biology, revealed that a protein called Importin-11 transports the cancer-causing protein beta-catenin into the nucleus of colon cancer cells, where it can drive cell proliferation.
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Inhibiting this transport step could block the growth of most colorectal cancers – also called bowel cancers – caused by elevated beta-catenin levels.
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Around 80 per cent of colorectal cancers are associated with mutations in a gene called APC that result in elevated levels of the beta-catenin protein.
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This increase in beta-catenin 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.
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But how beta-catenin enters the cell nucleus after its levels rise is poorly understood.
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“Because the molecular mechanisms underlying beta-catenin nuclear transport remain unclear, we set out to identify genes required for continuous beta-catenin activity in colorectal cancer cells harbouring APC mutations,” said Stephane Angers, Professor at the University of Toronto in Canada.
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Using CRISPR DNA editing technology, the researchers developed a new technique that allowed them to screen the human genome for genes that support beta-catenin’s activity in colorectal cancer cells after its levels have been elevated by mutations in APC.
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Angers and colleagues found that Importin-11 binds to beta-catenin and escorts it into the nucleus of colorectal cancer cells with mutations in APC. Removing Importin-11 from these cells prevented beta-catenin from entering the nucleus and activating its target genes.
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The researchers discovered that Importin-11 levels are often elevated in human colorectal cancers. Moreover, removing Importin-11 inhibited the growth of tumours formed by APC mutant cancer cells isolated from patients.
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“We conclude that Importin-11 is required for the growth of colorectal cancer cells,” Angers said.
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Learning more about how Importin-11 transports beta-catenin into the nucleus may help researchers develop new therapies that block this process and reduce the growth of colorectal cancers caused by mutations in APC.
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