Cell differentiation within a yeast colony: metabolic and regulatory parallels with a tumor-affected organism

Mol Cell. 2012 May 25;46(4):436-48. doi: 10.1016/j.molcel.2012.04.001. Epub 2012 May 3.

Abstract

Nutrient sensing and metabolic reprogramming are crucial for metazoan cell aging and tumor growth. Here, we identify metabolic and regulatory parallels between a layered, multicellular yeast colony and a tumor-affected organism. During development, a yeast colony stratifies into U and L cells occupying the upper and lower colony regions, respectively. U cells activate a unique metabolism controlled by the glutamine-induced TOR pathway, amino acid-sensing systems (SPS and Gcn4p) and signaling from mitochondria with lowered respiration. These systems jointly modulate U cell physiology, which adapts to nutrient limitations and utilize the nutrients released from L cells. Stress-resistant U cells share metabolic pathways and other similar characteristics with tumor cells, including the ability to proliferate. L cells behave similarly to stressed and starving cells, which activate degradative mechanisms to provide nutrients to U cells. Our data suggest a nutrient flow between both cell types, resembling the Cori cycle and glutamine-NH(4)(+) shuttle between tumor and healthy metazoan cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems / genetics
  • Amino Acids / metabolism
  • Animals
  • Autophagy
  • Cell Division
  • Gene Knockout Techniques
  • Genes, Fungal
  • Humans
  • Metabolic Networks and Pathways
  • Models, Biological
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Oxygen Consumption
  • Quaternary Ammonium Compounds / metabolism
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Signal Transduction
  • Stress, Physiological
  • Transcriptome

Substances

  • Amino Acid Transport Systems
  • Amino Acids
  • Quaternary Ammonium Compounds
  • Saccharomyces cerevisiae Proteins

Associated data

  • GEO/GSE35887