The fatal attraction between pro-prion and filamin A: prion as a marker in human cancers

Biomark Med. 2010 Jun;4(3):453-64. doi: 10.2217/bmm.10.14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Contractile Proteins / metabolism*
  • Cytoskeleton
  • Dimerization
  • Filamins
  • Humans
  • Melanoma / metabolism
  • Microfilament Proteins / metabolism*
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / metabolism*
  • Prions / metabolism*
  • Protein Precursors / metabolism*
  • Signal Transduction

Substances

  • Biomarkers, Tumor
  • Contractile Proteins
  • Filamins
  • Microfilament Proteins
  • Prions
  • Protein Precursors