Glucose-regulated proteins in cancer: molecular mechanisms and therapeutic potential

Nat Rev Cancer. 2014 Apr;14(4):263-76. doi: 10.1038/nrc3701.

Abstract

The glucose-regulated proteins (GRPs) are stress-inducible chaperones that mostly reside in the endoplasmic reticulum or the mitochondria. Recent advances show that the GRPs have functions that are distinct from those of the related heat shock proteins, and they can be actively translocated to other cellular locations and assume novel functions that control signalling, proliferation, invasion, apoptosis, inflammation and immunity. Mouse models further identified their specific roles in development, tumorigenesis, metastasis and angiogenesis. This Review describes their discovery and regulation, as well as their biological functions in cancer. Promising agents that use or target the GRPs are being developed, and their efficacy as anticancer therapeutics is also discussed.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Cell Proliferation
  • Drug Resistance, Neoplasm
  • Endoplasmic Reticulum / metabolism
  • Gene Expression Regulation, Neoplastic
  • HSP70 Heat-Shock Proteins / antagonists & inhibitors
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • Humans
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mitochondria / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplastic Stem Cells / metabolism
  • Stress, Physiological

Substances

  • Antineoplastic Agents
  • HSP70 Heat-Shock Proteins
  • Membrane Proteins
  • glucose-regulated proteins