Endoplasmic Reticulum Stress and Cancer: Could Unfolded Protein Response Be a Druggable Target for Cancer Therapy?

Int J Mol Sci. 2023 Jan 13;24(2):1566. doi: 10.3390/ijms24021566.

Abstract

Unfolded protein response (UPR) is an adaptive response which is used for re-establishing protein homeostasis, and it is triggered by endoplasmic reticulum (ER) stress. Specific ER proteins mediate UPR activation, after dissociation from chaperone Glucose-Regulated Protein 78 (GRP78). UPR can decrease ER stress, producing an ER adaptive response, block UPR if ER homeostasis is restored, or regulate apoptosis. Some tumour types are linked to ER protein folding machinery disturbance, highlighting how UPR plays a pivotal role in cancer cells to keep malignancy and drug resistance. In this review, we focus on some molecules that have been revealed to target ER stress demonstrating as UPR could be a new target in cancer treatment.

Keywords: ER stress; GRP78; UPR; natural compounds.

Publication types

  • Review

MeSH terms

  • Apoptosis
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum Chaperone BiP*
  • Endoplasmic Reticulum Stress
  • Heat-Shock Proteins / metabolism
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Unfolded Protein Response

Substances

  • Endoplasmic Reticulum Chaperone BiP
  • Heat-Shock Proteins

Grants and funding

This research received no external funding.