Small molecule activation of PKM in cancer cells induces serine auxotrophy

ABSTRACT: Proliferating tumor cells use aerobic glycolysis to support their high metabolic demands. Paradoxically, increased glycolysis is often accompanied by expression of the lower activity PKM isoform, effectively constraining lower glycolysis. Here, we report the discovery of novel PKM 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. PKM activation resulted in a metabolic rewiring of cancer cells manifested by a profound dependency on the non-essential amino acid serine for continued cell proliferation. Induction of serine auxotrophy by PKM activation was accompanied by reduced carbon flow into the serine biosynthetic pathway and increased expression of hig

ORGANISM(S): Homo sapiens

SUBMITTER: Charles Kung 

PROVIDER: E-GEOD-40191 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress