Metabolic scavenging by cancer cells: when the going gets tough, the tough keep eating

Br J Cancer. 2016 Sep 6;115(6):635-40. doi: 10.1038/bjc.2016.256. Epub 2016 Aug 18.

Abstract

Cancer is fundamentally a disease of uncontrolled cell proliferation. Tumour metabolism has emerged as an exciting new discipline studying how cancer cells obtain the necessary energy and cellular 'building blocks' to sustain growth. Glucose and glutamine have long been regarded as the key nutrients fuelling tumour growth. However, the inhospitable tumour microenvironment of certain cancers, like pancreatic cancer, causes the supply of these nutrients to be chronically insufficient for the demands of proliferating cancer cells. Recent work has shown that cancer cells are able to overcome this nutrient insufficiency by scavenging alternative substrates, particularly proteins and lipids. Here, we review recent work identifying the endocytic process of macropinocytosis and subsequent lysosomal processing as an important substrate-acquisition route. In addition, we discuss the impact of hypoxia on fatty acid metabolism and the relevance of exogenous lipids for supporting tumour growth as well as the routes by which tumour cells can access these lipids. Together, these cancer-specific scavenging pathways provide a promising opportunity for therapeutic intervention.

Publication types

  • Review

MeSH terms

  • Animals
  • Autophagy
  • Cell Division
  • Cell Hypoxia
  • Energy Metabolism
  • Fatty Acids / metabolism
  • Humans
  • Lipid Metabolism
  • Macromolecular Substances / metabolism
  • Metabolomics
  • Neoplasm Proteins / metabolism
  • Neoplasm Proteins / physiology
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Phosphatidylinositol 3-Kinases / physiology
  • Pinocytosis / physiology
  • Proto-Oncogene Proteins c-akt / physiology
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases / physiology

Substances

  • Fatty Acids
  • Macromolecular Substances
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases