title: Nuclear translocation of the tumor marker pyruvate kinase M2 induces programmed cell death.
abstract: Cancer cells often fail to respond to stimuli that normally activate their intrinsic apoptotic machinery. Moreover, they are able to adapt to hypoxia by changing their glycolytic rate. Pyruvate kinase (PK) is a rate-limiting enzyme in glycolysis that is converted to a less active dimer form of PKM2 isoenzyme during oncogenesis. Here, we show that both somatostatin and the structural analogue TT-232 interact with the PKM subtype. We further show that the PKM2 is translocated to the nucleus in response to TT-232 and different apoptotic agents. Nuclear translocation of PKM2 is sufficient to induce cell death that is caspase independent, isoform specific, and independent of its enzymatic activity. These results show that the tumor marker PKM2 plays a general role in caspase-independent cell death of tumor cells and thereby defines this glycolytic enzyme as a novel target for cancer therapy development.
authors.affiliation: Department of Molecular Biology, Max-Planck-Institute for Biochemistry, Martinsried, Germany. stetak@zool.unizh.ch
authors.forename: Attila
authors.initials: A
authors.lastname: Steták
authors.forename: Réka
authors.initials: R
authors.lastname: Veress
authors.forename: Judit
authors.initials: J
authors.lastname: Ovádi
authors.forename: Péter
authors.initials: P
authors.lastname: Csermely
authors.forename: György
authors.initials: G
authors.lastname: Kéri
authors.forename: Axel
authors.initials: A
authors.lastname: Ullrich
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019556:COS Cells; D002467:Cell Nucleus / Q000201:enzymology; D002522:Chlorocebus aethiops; D019281:Dimerization; D006801:Humans; D011770:Pyruvate Kinase / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D017481:Receptors, Somatostatin; C094462:TT2-32; D013004:Somatostatin; D011770:Pyruvate Kinase