Scientists Implicate Prion Protein in Aggressive Pancreatic Cancer

Scientists have discovered an incompletely processed form of the prion protein in pancreatic cancer that could represent both a biomarker and potentially a therapeutic target against the disease. The researchers at Case Western Reserve University School of Medicine identified this ‘pro-prion’ in a subpopulation of pancreatic cancer patients that had much shorter survival times than patients without the prion, suggesting its role in the aggressiveness of the disease.

The Case Western team first identified the nonglycosylated and non-GPI-anchored form of the prion protein in human pancreatic cancer cells. The pro-prion, which did retain its GPI anchor peptide signal sequence, was shown to bind to filamin A, a molecule that normally regulates cytoskeletal processes and signaling.

Binding of the pro-prion protein to filamin A resulted in disruption of the cell’s organization and signaling and led to more aggressive tumor cell growth. The researchers found that when prion levels were reduced, tumor cells lost their ability to grow, both in tissue culture and in animals. 

The research appears in the September issue of the Journal of Clinical Investigation in an article titled “Binding of pro-prion to filamin A disrupts cytoskeleton and correlates with poor prognosis in pancreatic cancer.” The Case Western team now aim to see if this type of prion protein expression is seen in other types of cancer.