PI3K signaling-regulated metabolic reprogramming: From mechanism to application

Biochim Biophys Acta Rev Cancer. 2023 Sep;1878(5):188952. doi: 10.1016/j.bbcan.2023.188952. Epub 2023 Jul 25.

Abstract

Oncogenic signaling involved in tumor metabolic reprogramming. Tumorigenesis was not only determined by the mutations or deletion of oncogenes but also accompanied by the reprogramming of cellular metabolism. Metabolic alterations play a crucial regulatory role in the development and progression of tumors. Oncogenic PI3K/AKT signaling mediates the metabolic switch in cancer cells and immune cells in the tumor microenvironment. PI3K/AKT and its downstream effector branch off and connect to multiple steps of metabolism, such as glucose, lipids, and amino acids. Thus, PI3K inhibitor could effectively regulate metabolic pathway and impede the oncogenic process and some key metabolic proteins or critical enzymes also constitute biomarkers for tumor diagnosis and treatment. In the current review, we summarize the significant effect of PI3K/AKT signaling toward tumor metabolism, it enables us to obtain the better understanding for this interaction and develop more effective therapeutic strategies targeting cancer cell metabolism.

Keywords: Amino acid metabolism; Fatty acid metabolism; Glycolysis; Metabolic reprogramming; PI3K/AKT.

Publication types

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

MeSH terms

  • Humans
  • Neoplasms* / genetics
  • Oncogenes
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Tumor Microenvironment

Substances

  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt