title: Warburg meets autophagy: cancer-associated fibroblasts accelerate tumor growth and metastasis via oxidative stress, mitophagy, and aerobic glycolysis.
abstract: CONCLUSIONS
  Here, we review certain recent advances in oxidative stress and tumor metabolism, which are related to understanding the contributions of the microenvironment in promoting tumor growth and metastasis. In the early 1920s, Otto Warburg, a Nobel Laureate, formulated a hypothesis to explain the "fundamental basis" of cancer, based on his observations that tumors displayed a metabolic shift toward glycolysis. In 1963, Christian de Duve, another Nobel Laureate, first coined the phrase auto-phagy, derived from the Greek words "auto" and "phagy," meaning "self" and "eating."
  
  
  BACKGROUND
  Now, we see that these two ideas (autophagy and aerobic glycolysis) physically converge in the tumor stroma. First, cancer cells secrete hydrogen peroxide. Then, as a consequence, oxidative stress in cancer-associated fibroblasts drives autophagy, mitophagy, and aerobic glycolysis.
  
  
  RESULTS
  This "parasitic" metabolic coupling converts the stroma into a "factory" for the local production of recycled and high-energy nutrients (such as L-lactate)-to fuel oxidative mitochondrial metabolism in cancer cells. We believe that Warburg and de Duve would be pleased with this new two-compartment model for understanding tumor metabolism. It adds a novel stromal twist to two very well-established cancer paradigms: aerobic glycolysis and autophagy.
  
  
  CONCLUSIONS
  Undoubtedly, these new metabolic models will foster the development of novel biomarkers, and corresponding therapies, to achieve the goal of personalized cancer medicine. Given the central role that oxidative stress plays in this process, new powerful antioxidants should be developed in the fight against cancer.
authors: Department of Stem Cell Biology & Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, PA 19107, USA.
authors: Stephanos
authors: S
authors: Pavlides
authors: Iset
authors: I
authors: Vera
authors: Ricardo
authors: R
authors: Gandara
authors: Sharon
authors: S
authors: Sneddon
authors: Richard G
authors: RG
authors: Pestell
authors: Isabelle
authors: I
authors: Mercier
authors: Ubaldo E
authors: UE
authors: Martinez-Outschoorn
authors: Diana
authors: D
authors: Whitaker-Menezes
authors: Anthony
authors: A
authors: Howell
authors: Federica
authors: F
authors: Sotgia
authors: Michael P
authors: MP
authors: Lisanti
mesh_terms: D000332:Aerobiosis; D000818:Animals; D001343:Autophagy; D005347:Fibroblasts / Q000473:pathology; D006019:Glycolysis; D006801:Humans; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress