Molecular Connections between Cancer Cell Metabolism and the Tumor Microenvironment

Int J Mol Sci. 2015 May 15;16(5):11055-86. doi: 10.3390/ijms160511055.


Cancer cells preferentially utilize glycolysis, instead of oxidative phosphorylation, for metabolism even in the presence of oxygen. This phenomenon of aerobic glycolysis, referred to as the "Warburg effect", commonly exists in a variety of tumors. Recent studies further demonstrate that both genetic factors such as oncogenes and tumor suppressors and microenvironmental factors such as spatial hypoxia and acidosis can regulate the glycolytic metabolism of cancer cells. Reciprocally, altered cancer cell metabolism can modulate the tumor microenvironment which plays important roles in cancer cell somatic evolution, metastasis, and therapeutic response. In this article, we review the progression of current understandings on the molecular interaction between cancer cell metabolism and the tumor microenvironment. In addition, we discuss the implications of these interactions in cancer therapy and chemoprevention.

Keywords: acidosis; cancer cell metabolism; cancer therapy; hypoxia; tumor microenvironment.

Publication types

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

MeSH terms

  • Acidosis / metabolism
  • Acidosis / pathology
  • Glycolysis
  • Humans
  • Hypoxia
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Protein Kinase Inhibitors / therapeutic use
  • Tumor Microenvironment / genetics*


  • Protein Kinase Inhibitors