The impact of the endoplasmic reticulum protein-folding environment on cancer development

Nat Rev Cancer. 2014 Sep;14(9):581-97. doi: 10.1038/nrc3800.


The endoplasmic reticulum (ER) is an essential organelle in eukaryotic cells for the storage and regulated release of calcium and as the entrance to the secretory pathway. Protein misfolding in the ER causes accumulation of misfolded proteins (ER stress) and activation of the unfolded protein response (UPR), which has evolved to maintain a productive ER protein-folding environment. Both ER stress and UPR activation are documented in many different human cancers. In this Review, we summarize the impact of ER stress and UPR activation on every aspect of cancer and discuss outstanding questions for which answers will pave the way for therapeutics.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Endoplasmic Reticulum Stress*
  • Humans
  • Molecular Targeted Therapy / methods
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / physiopathology
  • Tumor Microenvironment*
  • Unfolded Protein Response*


  • Antineoplastic Agents