Cancer metabolism and the Warburg effect: the role of HIF-1 and PI3K

Rupert Courtnay, Darleen C. Ngo, Neha Malik, Katherine Ververis, Stephanie M. Tortorella, Tom C. Karagiannis

Research output: Contribution to journalReview ArticleResearchpeer-review

198 Citations (Scopus)

Abstract

Cancer cells have been shown to have altered metabolism when compared to normal non-malignant cells. The Warburg effect describes a phenomenon in which cancer cells preferentially metabolize glucose by glycolysis, producing lactate as an end product, despite being the presence of oxygen. The phenomenon was first described by Otto Warburg in the 1920s, and has resurfaced as a controversial theory, with both supportive and opposing arguments. The biochemical aspects of the Warburg effect outline a strong explanation for the cause of cancer cell proliferation, by providing the biological requirements for a cell to grow. Studies have shown that pathways such as phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) as well as hypoxia inducible factor-1 (HIF-1) are central regulators of glycolysis, cancer metabolism and cancer cell proliferation. Studies have shown that PI3K signaling pathways have a role in many cellular processes such as metabolism, inflammation, cell survival, motility and cancer progression. Herein, the cellular aspects of the PI3K pathway are described, as well as the influence HIF has on cancer cell metabolism. HIF-1 activation has been related to angiogenesis, erythropoiesis and modulation of key enzymes involved in aerobic glycolysis, thereby modulating key processes required for the Warburg effect. In this review we discuss the molecular aspects of the Warburg effect with a particular emphasis on the role of the HIF-1 and the PI3K pathway.

Original languageEnglish
Pages (from-to)841-851
Number of pages11
JournalMolecular Biology Reports
Volume42
Issue number4
DOIs
Publication statusPublished - Apr 2015
Externally publishedYes

Keywords

  • Warburg effect
  • Cancer metabolism
  • Glucose metabolism
  • Glycolysis
  • HIF-1
  • PI3K

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