Autophagy and cancer stem cells: molecular mechanisms and therapeutic applications

Cell Death Differ. 2019 Mar;26(4):690-702. doi: 10.1038/s41418-019-0292-y. Epub 2019 Feb 6.

Abstract

Autophagy and mitophagy act in cancer as bimodal processes, whose differential functions strictly depend on cancer ontogenesis, progression, and type. For instance, they can act to promote cancer progression by helping cancer cells survive stress or, instead, when mutated or abnormal, to induce carcinogenesis by influencing cell signaling or promoting intracellular toxicity. For this reason, the study of autophagy in cancer is the main focus of many researchers and several clinical trials are already ongoing to manipulate autophagy and by this way determine the outcome of disease therapy. Since the establishment of the cancer stem cell (CSC) theory and the discovery of CSCs in individual cancer types, autophagy and mitophagy have been proposed as key mechanisms in their homeostasis, dismissal or spread, even though we still miss a comprehensive view of how and by which regulatory molecules these two processes drive cell fate. In this review, we will dive into the deep water of autophagy, mitophagy, and CSCs and offer novel viewpoints on possible therapeutic strategies, based on the modulation of these degradative systems.

Publication types

  • Review

MeSH terms

  • Animals
  • Autophagy / drug effects*
  • Autophagy / genetics*
  • Autophagy / immunology
  • Humans
  • Mitophagy / drug effects
  • Mitophagy / genetics
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / therapy
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / drug effects*
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / metabolism*
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Tumor Microenvironment / drug effects
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology