A new inactivation mechanism of a crucial tumour suppressor: investigating amyloid formation in cancer

Cancer is the leading cause of death in Aotearoa New Zealand. It contributes to approximately 30% of all deaths, with the incidence increasing as our population ages. Cancer involves uncontrolled cell growth and cell division. Tumour suppressors are proteins that strictly control cell division in healthy cells. These proteins are very often mutated in cancer cells, leading to uncontrolled cell division and tumour development. p16 is a tumour suppressor protein that is amongst the most frequently mutated in cancer patients. We recently discovered that under stress conditions, p16 can change its structure and forms large fibrillar aggregates called amyloid. In this amyloid state, p16 is unable to carry out its normal protective function. 

We will investigate this alternative p16 state by identifying which part of the protein is involved in amyloid formation, and if tumour-associated mutations promote amyloid formation. Amyloid proteins have been well studied in relation to dementias; our study will be the first to characterise amyloid proteins involved in cancer, promising novel insights into tumour biology. A thorough understanding of how these proteins function and the mechanisms cancers use to inactivate tumour suppressors will be crucial for development of novel treatments.