title: The fatal attraction between pro-prion and filamin A: prion as a marker in human cancers.
abstract: Pancreatic cancer is the fourth leading cancer causing deaths in the USA, with more than 30,000 deaths per year. The overall median survival for all pancreatic cancer is 6 months and the 5-year survival rate is less than 10%. This dismal outcome reflects the inefficacy of the chemotherapeutic agents, as well as the lack of an early diagnostic marker. A protein known as prion (PrP) is expressed in human pancreatic cancer cell lines. However, in these cell lines, the PrP is incompletely processed and exists as pro-PrP. The pro-PrP binds to a molecule inside the cell, filamin A (FLNa), which is an integrator of cell signaling and mechanics. The binding of pro-PrP to FLNa disrupts the normal functions of FLNa, altering the cell's cytoskeleton and signal transduction machineries. As a result, the tumor cells grow more aggressively. Approximately 40% of patients with pancreatic cancer express PrP in their cancer. These patients have significantly shorter survival compared with patients whose pancreatic cancers lack PrP. Therefore, expression of pro-PrP and its binding to FLNa provide a growth advantage to pancreatic cancers. In this article, we discuss the following points: the biology of PrP, the consequences of binding of pro-PrP to FLNa in pancreatic cancer, the detection of pro-PrP in other cancers, the potential of using pro-PrP as a diagnostic marker, and prevention of the binding between pro-PrP and FLNa as a target for therapeutic intervention in cancers.
authors.affiliation: Department of Pathology, School of Medicine, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA. man-sun.sy@case.edu
authors.forename: Man-Sun
authors.initials: MS
authors.lastname: Sy
authors.forename: Chaoyang
authors.initials: C
authors.lastname: Li
authors.forename: Shuiliang
authors.initials: S
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Xin
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D003285:Contractile Proteins / Q000378:metabolism*; D003599:Cytoskeleton; D019281:Dimerization; D064448:Filamins; D006801:Humans; D008545:Melanoma / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins; D011328:Prions; D011498:Protein Precursors