NMR metabolomics highlights sphingosine kinase-1 as a new molecular switch in the orchestration of aberrant metabolic phenotype in cancer cells

Mol Oncol. 2017 May;11(5):517-533. doi: 10.1002/1878-0261.12048. Epub 2017 Mar 30.


Strong experimental evidence in animal and cellular models supports a pivotal role of sphingosine kinase-1 (SK1) in oncogenesis. In many human cancers, SK1 levels are upregulated and these increases are linked to poor prognosis in patients. Here, by employing untargeted NMR-based metabolomic profiling combined with functional validations, we report the crucial role of SK1 in the metabolic shift known as the Warburg effect in A2780 ovarian cancer cells. Indeed, expression of SK1 induced a high glycolytic rate, characterized by increased levels of lactate along with increased expression of the proton/monocarboxylate symporter MCT1, and decreased oxidative metabolism, associated with the accumulation of intermediates of the tricarboxylic acid cycle and reduction in CO2 production. Additionally, SK1-expressing cells displayed a significant increase in glucose uptake paralleled by GLUT3 transporter upregulation. The role of SK1 is not limited to the induction of aerobic glycolysis, affecting metabolic pathways that appear to support the biosynthesis of macromolecules. These findings highlight the role of SK1 signaling axis in cancer metabolic reprogramming, pointing out innovative strategies for cancer therapies.

Keywords: NMR-based metabolomics; Warburg effect; ovarian cancer; sphingosine kinase-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Animals
  • Carbon Dioxide / metabolism
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Female
  • Glucose / metabolism
  • Glucose Transporter Type 3 / metabolism
  • Glycolysis* / drug effects
  • Humans
  • Lactic Acid / analysis
  • Lactic Acid / metabolism
  • Magnetic Resonance Imaging / methods*
  • Metabolomics / methods*
  • Mitochondria / metabolism
  • Oncogene Proteins / metabolism
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Oxidation-Reduction / drug effects
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / pharmacology*
  • Prognosis
  • Tricarboxylic Acids / metabolism
  • Up-Regulation


  • Cell Cycle Proteins
  • Glucose Transporter Type 3
  • MCTS1 protein, human
  • Oncogene Proteins
  • SLC2A3 protein, human
  • Tricarboxylic Acids
  • Carbon Dioxide
  • Lactic Acid
  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase
  • Glucose