New Insights in ATP Synthesis as Therapeutic Target in Cancer and Angiogenic Ocular Diseases

Cornelis J.F. van Noorden*, Bahar Yetkin-Arik, Paola Serrano Martinez, Noëlle Bakker, Mathilda E. van Breest Smallenburg, Reinier O. Schlingemann, Ingeborg Klaassen, Bernarda Majc, Anamarija Habic, Urban Bogataj, S. Katrin Galun, Milos Vittori, Mateja Erdani Kreft, Metka Novak, Barbara Breznik, Vashendriya V.V. Hira

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Abstract

Lactate and ATP formation by aerobic glycolysis, the Warburg effect, is considered a hallmark of cancer. During angiogenesis in non-cancerous tissue, proliferating stalk endothelial cells (ECs) also produce lactate and ATP by aerobic glycolysis. In fact, all proliferating cells, both non-cancer and cancer cells, need lactate for the biosynthesis of building blocks for cell growth and tissue expansion. Moreover, both non-proliferating cancer stem cells in tumors and leader tip ECs during angiogenesis rely on glycolysis for pyruvate production, which is used for ATP synthesis in mitochondria through oxidative phosphorylation (OXPHOS). Therefore, aerobic glycolysis is not a specific hallmark of cancer but rather a hallmark of proliferating cells and limits its utility in cancer therapy. However, local treatment of angiogenic eye conditions with inhibitors of glycolysis may be a safe therapeutic option that warrants experimental investigation. Most types of cells in the eye such as photoreceptors and pericytes use OXPHOS for ATP production, whereas proliferating angiogenic stalk ECs rely on glycolysis for lactate and ATP production. (J Histochem Cytochem XX.XXX–XXX,

Original languageEnglish
Pages (from-to)329-352
Number of pages24
JournalJournal of Histochemistry and Cytochemistry
Volume72
Issue number5
DOIs
Publication statusPublished - May 2024

Keywords

  • aerobic glycolysis
  • anaerobic glycolysis
  • angiogenesis
  • ATP synthesis
  • cancer cells
  • cancer stem cells
  • endothelial cells
  • energy metabolism
  • eye diseases
  • oxidative phosphorylation
  • pericytes
  • retina
  • Warburg effect

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