Small molecule activation of pkm2 in cancer cells induces serine auxotrophy Academic Article uri icon


MeSH Major

  • Carrier Proteins
  • Membrane Proteins
  • Serine
  • Small Molecule Libraries
  • Thyroid Hormones


  • Proliferating tumor cells use aerobic glycolysis to support their high metabolic demands. Paradoxically, increased glycolysis is often accompanied by expression of the lower activity PKM2 isoform, effectively constraining lower glycolysis. Here, we report the discovery of PKM2 activators with a unique allosteric binding mode. Characterization of how these compounds impact cancer cells revealed an unanticipated link between glucose and amino acid metabolism. PKM2 activation resulted in a metabolic rewiring of cancer cells manifested by a profound dependency on the nonessential amino acid serine for continued cell proliferation. Induction of serine auxotrophy by PKM2 activation was accompanied by reduced carbon flow into the serine biosynthetic pathway and increased expression of high affinity serine transporters. These data support the hypothesis that PKM2 expression confers metabolic flexibility to cancer cells that allows adaptation to nutrient stress.

publication date

  • September 21, 2012



  • Academic Article



  • eng

PubMed Central ID

  • PMC3775715

Digital Object Identifier (DOI)

  • 10.1016/j.chembiol.2012.07.021

PubMed ID

  • 22999886

Additional Document Info

start page

  • 1187

end page

  • 98


  • 19


  • 9