Metabolic Changes Associated With Tumor Metastasis, Part 1: Tumor pH, Glycolysis and the Pentose Phosphate Pathway

Cell Mol Life Sci. 2016 Apr;73(7):1333-48. doi: 10.1007/s00018-015-2098-5. Epub 2015 Dec 1.

Abstract

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.

Keywords: Glycolysis; Lactate; Pentose phosphate pathway (PPP); Phosphoglucose isomerase (PGI); Tumor metastasis; Tumor pH.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Epithelial-Mesenchymal Transition
  • Glucose-6-Phosphate Isomerase / metabolism
  • Glycolysis
  • Humans
  • Lactic Acid / metabolism
  • Neoplasm Metastasis
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Pentose Phosphate Pathway / physiology*

Substances

  • Lactic Acid
  • Glucose-6-Phosphate Isomerase