Cellular and Molecular Life Sciences

, Volume 73, Issue 7, pp 1333–1348 | Cite as

Metabolic changes associated with tumor metastasis, part 1: tumor pH, glycolysis and the pentose phosphate pathway

  • Valéry L. Payen
  • Paolo E. Porporato
  • Bjorn Baselet
  • Pierre Sonveaux


Metabolic adaptations are intimately associated with changes in cell behavior. Cancers are characterized by a high metabolic plasticity resulting from mutations and the selection of metabolic phenotypes conferring growth and invasive advantages. While metabolic plasticity allows cancer cells to cope with various microenvironmental situations that can be encountered in a primary tumor, there is increasing evidence that metabolism is also a major driver of cancer metastasis. Rather than a general switch promoting metastasis as a whole, a succession of metabolic adaptations is more likely needed to promote different steps of the metastatic process. This review addresses the contribution of pH, glycolysis and the pentose phosphate pathway, and a companion paper summarizes current knowledge regarding the contribution of mitochondria, lipids and amino acid metabolism. Extracellular acidification, intracellular alkalinization, the glycolytic enzyme phosphoglucose isomerase acting as an autocrine cytokine, lactate and the pentose phosphate pathway are emerging as important factors controlling cancer metastasis.


Tumor metastasis Tumor pH Glycolysis Phosphoglucose isomerase (PGI) Lactate Pentose phosphate pathway (PPP) 



6-Phosphogluconate dehydrogenase


Anion exchanger 2


Autocrine motility factor = PGI


Activator protein-1


Carbonic anhydrase


Circulating tumor cell


Extracellular matrix


Epithelial-to-mesenchymal transition


Electron transport chain


Hepatocyte growth factor


Hypoxia-inducible factor-1


Hyaluronidase 2




Lactate dehydrogenase


Mitogen-activated protein kinase


Monocarboxylate transporter




Matrix metalloproteinase


Membrane-type 1 matrix metalloproteinase


Nuclear factor-κB


Sodium-proton exchanger


Phosphoglucose isomerase = AMF


Prolyl-hydroxylase 2


Extracellular pH


Intracellular pH


Pyruvate kinase M


Pentose phosphate pathway


Reactive oxygen species




Transketolase-like 1




Vascular endothelial growth factor



Work at the authors’ lab is supported by a Starting Grant from the European Research Council (ERC No. 243188 TUMETABO), Interuniversity Attraction Pole (IAP) grant #UP7-03 from the Belgian Science Policy Office (Belspo), an Action de Recherche Concertée from the Communauté Française de Belgique (ARC 14/19-058), the Belgian Fonds National de la Recherche Scientifique (F.R.S.-FNRS), the Télévie, the Belgian Fondation contre le Cancer (2012-186), the Belgian Federal Agency for Nuclear Control (FANC-AFCN), the Louvain Foundation and the UCL Fonds Spéciaux de la Recherche (FSR). Pierre Sonveaux is a F.R.S.-FNRS Research Associate, Paolo E. Porporato a F.R.S.-FNRS Postdoctoral Fellow and Valéry L. Payen a F.R.S.-FNRS PhD Fellow. Bjorn Baselet is a grantee of the Belgian Nuclear Research Center (SCK∙CEN).


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Copyright information

© Springer International Publishing 2015

Authors and Affiliations

  • Valéry L. Payen
    • 1
  • Paolo E. Porporato
    • 1
  • Bjorn Baselet
    • 1
    • 2
  • Pierre Sonveaux
    • 1
  1. 1.Pole of Pharmacology, Institut de Recherche Expérimentale et Clinique (IREC)Université catholique de Louvain (UCL)BrusselsBelgium
  2. 2.Radiobiology Unit, Belgian Nuclear Research Centre, SCK∙CENMolBelgium

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