Endoplasmic reticulum stress signals in the tumour and its microenvironment. Review uri icon

Overview

abstract

  • Protein handling, modification and folding in the endoplasmic reticulum (ER) are tightly regulated processes that determine cell function, fate and survival. In several tumour types, diverse oncogenic, transcriptional and metabolic abnormalities cooperate to generate hostile microenvironments that disrupt ER homeostasis in malignant and stromal cells, as well as infiltrating leukocytes. These changes provoke a state of persistent ER stress that has been demonstrated to govern multiple pro-tumoural attributes in the cancer cell while dynamically reprogramming the function of innate and adaptive immune cells. Aberrant activation of ER stress sensors and their downstream signalling pathways have therefore emerged as key regulators of tumour growth and metastasis as well as response to chemotherapy, targeted therapies and immunotherapy. In this Review, we discuss the physiological inducers of ER stress in the tumour milieu, the interplay between oncogenic signalling and ER stress response pathways in the cancer cell and the profound immunomodulatory effects of sustained ER stress responses in tumours.

publication date

  • November 19, 2020

Research

keywords

  • Endoplasmic Reticulum
  • Endoplasmic Reticulum Stress
  • Neoplasms
  • Tumor Microenvironment
  • Unfolded Protein Response

Identity

PubMed Central ID

  • PMC7927882

Scopus Document Identifier

  • 85096343189

Digital Object Identifier (DOI)

  • 10.1200/PO.16.00073

PubMed ID

  • 33214692

Additional Document Info

volume

  • 21

issue

  • 2