Dissecting the Role of Autophagy-Related Proteins in Cancer Metabolism and Plasticity

Cells. 2023 Oct 19;12(20):2486. doi: 10.3390/cells12202486.

Abstract

Modulation of autophagy as an anticancer strategy has been widely studied and evaluated in several cell models. However, little attention has been paid to the metabolic changes that occur in a cancer cell when autophagy is inhibited or induced. In this review, we describe how the expression and regulation of various autophagy-related (ATGs) genes and proteins are associated with cancer progression and cancer plasticity. We present a comprehensive review of how deregulation of ATGs affects cancer cell metabolism, where inhibition of autophagy is mainly reflected in the enhancement of the Warburg effect. The importance of metabolic changes, which largely depend on the cancer type and form part of a cancer cell's escape strategy after autophagy modulation, is emphasized. Consequently, pharmacological strategies based on a dual inhibition of metabolic and autophagy pathways emerged and are reviewed critically here.

Keywords: Warburg effect; aerobic glycolysis; autophagy; autophagy-related (ATGs) genes/proteins; cancer cell metabolism; cancer plasticity; fatty acid oxidation (FAO); tumor microenvironment.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy-Related Proteins / metabolism
  • Glycolysis*
  • Humans
  • Neoplasms* / metabolism
  • Oxidative Stress

Substances

  • Autophagy-Related Proteins

Grants and funding

This study was funded by the Mexican National Council of Science and Technology (CONACyT) programs (PRONACES #303072, CF-2019 21887, FOP02-2022-02 321696).