University of Otago researchers have discovered a new function of a tumour-suppressing protein, which could help scientists develop better cancer treatment options and improve the diagnosis of various cancers in the future.
The research, published today in the British scientific journal Nature Communications — led by Christoph Goebl from the Department of Pathology and Biomedical Science — centres on the p16 protein which is well-known for stopping tumours from forming by preventing uncontrolled cell division.
However, it has now been discovered that once the protein changes to what's known as the amyloid (or dysfunctional) state, it loses this protective function and can allow cancerous tumours to form.
"What we found now is that p16, which is a tumour-related protein, can also form those amyloids ... once it is in this aggregated state, it is inactive and not able to prevent cell division anymore. And that's exactly when it loses its important protective function," Goebl told 1News.
P16 is among the top five proteins found to be mutated in various cancers, with the ability to actively cause certain types of cancer when damaged, he said.
Goebl said proteins that form amyloids were also associated with neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease.
Goebl said interestingly once the protein is oxidised and in the amyloid state, it can then be disassembled and "switched back to normal" by reversing its oxidation.
"Therefore, the team was able to discover a redox-based amyloid system which can switch between its normal state and the amyloid state by creating or breaking one chemical bond.
"The protein can choose whether it wants to go into the active or inactive state, and we think that that cancers exploit that functionality."
He stressed that while this discovery is only a "basic biology finding" and not a clinical study, the many years testing p16 in the laboratory would help scientists understand the structure of cancer better and inform future cures.
"It's so important to understand the basis of cancer, and only then can we really adjust our treatments and find new treatment options.
"This discovery has the potential to guide the development of novel treatment options and improved diagnostic procedures for various cancers."
Where to next?
With further support from the Health Research Council of New Zealand, alongside fresh funding from the Canterbury Research Medical Foundation and the Cancer Research Trust, the team were now studying this structural transition and how it worked in several different types of cancer cells.
Goebl said the next step for global researchers, and his team, would be looking at at how to stabilise the protein for future use.
"Ideally, we could develop some molecules — small molecules — that would stabilise the protein and thereby keeping it in the active state, keeping it from preventing uncontrolled cell division – that's one of our long-term goals."
Goebl said in the short term, he hoped this breakthrough would "expand the toolbox" available to oncologists and help them to pick the best drug for a specific patient, as it adds a variable to the testing process.
"If we can characterise tumours, we can look at the p16 state now and ideally, we can find correlations and say, 'treatment A is better if p16 is in this amyloid state versus treatment B'."
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