The fatal attraction between pro-prion and filamin A: prion as a marker in human cancers.
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.
Sy
Man-Sun
MS
Department of Pathology, School of Medicine, Case Western Reserve University, 2103 Cornell Road, Cleveland, OH 44106, USA. man-sun.sy@case.edu
Li
Chaoyang
C
Yu
Shuiliang
S
Xin
Wei
W
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
D014408:Biomarkers, Tumor; D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins; D011328:Prions; D011498:Protein Precursors