Mitochondrial Stress Response and Cancer

Trends Cancer. 2020 Aug;6(8):688-701. doi: 10.1016/j.trecan.2020.04.009. Epub 2020 May 22.

Abstract

Cancer cells survive and adapt to many types of stress including hypoxia, nutrient deprivation, metabolic, and oxidative stress. These stresses are sensed by diverse cellular signaling processes, leading to either degradation of mitochondria or alleviation of mitochondrial stress. This review discusses signaling during sensing and mitigation of stress involving mitochondrial communication with the endoplasmic reticulum, and how retrograde signaling upregulates the mitochondrial stress response to maintain mitochondrial integrity. The importance of the mitochondrial unfolded protein response, an emerging pathway that alleviates cellular stress, will be elaborated with respect to cancer. Detailed understanding of cellular pathways will establish mitochondrial stress response as a key mechanism for cancer cell survival leading to cancer progression and resistance, and provide a potential therapeutic target in cancer.

Keywords: cancer cell survival; cancer progression; heat shock protein 60; mitochondrial stress response; mitochondrial unfolded protein response; therapeutic resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Activating Transcription Factors / metabolism
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Survival / drug effects
  • Chaperonin 60 / metabolism
  • Disease Progression
  • Drug Resistance, Neoplasm / drug effects
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / pathology
  • Endoplasmic Reticulum Stress / drug effects
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / pathology*
  • Mitochondrial Proteins / metabolism
  • Neoplasms / drug therapy
  • Neoplasms / pathology*
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Unfolded Protein Response / drug effects*

Substances

  • ATF5 protein, human
  • Activating Transcription Factors
  • Antineoplastic Agents
  • Chaperonin 60
  • HSPD1 protein, human
  • Mitochondrial Proteins
  • Reactive Oxygen Species