To betray or to fight? The dual identity of the mitochondria in cancer

Future Oncol. 2021 Feb;17(6):723-743. doi: 10.2217/fon-2020-0362. Epub 2021 Jan 18.

Abstract

Mitochondria are highly dynamic organelles that provide energy for oxidative phosphorylation in cells. Equally, they are the major sites for the metabolism of amino acids, lipids and iron. When cells become cancerous, the morphology, cellular location and metabolic mode of the mitochondria change accordingly. These mitochondrial changes can have two opposing effects on cancer: procancer and anticancer effects. Specifically, mitochondria play roles in the fight against cancer by participating in processes such as ferroptosis, mitophagy and antitumor immunity. Contrastingly, cancer cells can also enslave mitochondria to give them the conditions necessary for growth and metastasis. Moreover, through mitochondria, cancer cells can escape from immune surveillance, resulting in their immune escape and enhanced malignant transformation ability. At present, cancer-related studies of mitochondria are one-sided; therefore, we aim to provide a comprehensive understanding by systematically reviewing the two-sided cancer-related properties of mitochondria. Mitochondrial-targeted drugs are gradually emerging and showing significant advantages in cancer treatment; thus, our in-depth exploration of mitochondria in cancer will help to provide theoretical support for the future provision of efficient and low-toxicity cancer treatments.

Keywords: ROS; antitumor drugs; autophagy; cancer; dual character; ferroptosis; immune system; metabolic reprogramming; metastasis; migration; mitochondria.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Cell Transformation, Neoplastic / drug effects
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology
  • DNA, Mitochondrial / genetics
  • Ferroptosis / drug effects
  • Ferroptosis / genetics
  • Humans
  • Mitochondria / drug effects*
  • Mitochondria / immunology
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Mitophagy / drug effects*
  • Mitophagy / genetics
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Oxidative Phosphorylation / drug effects
  • Oxidative Stress / drug effects
  • Oxidative Stress / genetics
  • Reactive Oxygen Species / metabolism
  • Tumor Escape / drug effects
  • Warburg Effect, Oncologic / drug effects

Substances

  • Antineoplastic Agents
  • DNA, Mitochondrial
  • Reactive Oxygen Species