The PI3K/Akt Pathway and Glucose Metabolism: A Dangerous Liaison in Cancer.

1. Int J Biol Sci. 2024 May 27;20(8):3113-3125. doi: 10.7150/ijbs.89942. eCollection 2024. The PI3K/Akt Pathway and Glucose Metabolism: A Dangerous Liaison in Cancer. Fontana F(1), Giannitti G(1), Marchesi S(1), Limonta P(1). Author information: (1)Department of Pharmacological and Biomolecular Sciences "Rodolfo Paoletti", Università degli Studi di Milano, Milan, Italy. Aberrant activation of the PI3K/Akt pathway commonly occurs in cancers and correlates with multiple aspects of malignant progression. In particular, recent evidence suggests that the PI3K/Akt signaling plays a fundamental role in promoting the so-called aerobic glycolysis or Warburg effect, by phosphorylating different nutrient transporters and metabolic enzymes, such as GLUT1, HK2, PFKB3/4 and PKM2, and by regulating various molecular networks and proteins, including mTORC1, GSK3, FOXO transcription factors, MYC and HIF-1α. This leads to a profound reprogramming of cancer metabolism, also impacting on pentose phosphate pathway, mitochondrial oxidative phosphorylation, de novo lipid synthesis and redox homeostasis and thereby allowing the fulfillment of both the catabolic and anabolic demands of tumor cells. The present review discusses the interactions between the PI3K/Akt cascade and its metabolic targets, focusing on their possible therapeutic implications. © The author(s). DOI: 10.7150/ijbs.89942 PMCID: PMC11186371 PMID: 38904014 [Indexed for MEDLINE] Conflict of interest statement: Competing Interests: The authors have declared that no competing interest exists.