title: Oncophosphosignaling Favors a Glycolytic Phenotype in Human Drug Resistant Leukemia.
abstract: In chemoresistant leukemia cells (Lucena-1), the low molecular weight protein tyrosine phosphatase (LMWPTP) is about 20-fold more active than in their susceptible counterpart (K562). We found this phosphatase ensures the activated statuses of Src and Bcr-Abl. Since, phosphorylation and dephosphorylation of proteins represent a key post-translational regulation of several enzymes, we also explored the kinome. We hereby show that LMWPTP superactivation, together with kinome reprogramming, cooperate towards glucose addiction. Resistant leukemia cells present lower levels of oxidative metabolism, in part due to downexpression of the following mitochondrial proteins: pyruvate dehydrogenase subunit alpha 1, succinate dehydrogenase, and voltage-dependent anion channel. Those cells displayed higher expression levels of glucose transporter 1 and higher production of lactate. In addition, Lucena-1 siRNA LMWPTP cells showed lower expression levels of glucose transporter 1 and lower activity of lactate dehydrogenase. On the other hand, K562 cells overexpressing LMWPTP presented higher expression/activity of both proteins. In this study, we show that LMWPTP is a pivotal mediator of metabolic reprogramming that confers survival advantages to leukemia cells against death stimuli. J. Cell. Biochem. 118: 3846-3854, 2017. © 2017 Wiley Periodicals, Inc.
authors.affiliation: Department of Biochemistry and Tissue Biology, Biology Institute, University of Campinas, Campinas, São Paulo 13083-862, Brazil.
authors.forename: Alessandra V S
authors.identifier: 0000-0003-1161-5724
authors.initials: AVS
authors.lastname: Faria
authors.affiliation: Department of Biochemistry and Tissue Biology, Biology Institute, University of Campinas, Campinas, São Paulo 13083-862, Brazil.
authors.forename: Thaís F
authors.initials: TF
authors.lastname: Tornatore
authors.affiliation: Department of Biochemistry and Tissue Biology, Biology Institute, University of Campinas, Campinas, São Paulo 13083-862, Brazil.
authors.forename: Renato
authors.initials: R
authors.lastname: Milani
authors.affiliation: Department of Biochemistry and Tissue Biology, Biology Institute, University of Campinas, Campinas, São Paulo 13083-862, Brazil.
authors.forename: Karla C S
authors.initials: KCS
authors.lastname: Queiroz
authors.affiliation: Department of Structural and Functional Biology, University of Campinas, Campinas, São Paulo 13083-862, Brazil.|Faculty of Medicine of Ribeirão Preto, Department of Biochemistry and Immunology, University of São Paulo, Ribeirão Preto, São Paulo 14049-900, Brazil.
authors.forename: Igor H
authors.initials: IH
authors.lastname: Sampaio
authors.affiliation: Department of Biochemistry and Tissue Biology, Biology Institute, University of Campinas, Campinas, São Paulo 13083-862, Brazil.
authors.forename: Emanuella M B
authors.initials: EMB
authors.lastname: Fonseca
authors.forename: Karin J P
authors.initials: KJP
authors.lastname: Rocha-Brito
authors.affiliation: Department of Biochemistry and Tissue Biology, Biology Institute, University of Campinas, Campinas, São Paulo 13083-862, Brazil.
authors.forename: Tamira O
authors.initials: TO
authors.lastname: Santos
authors.affiliation: Department of Structural and Functional Biology, University of Campinas, Campinas, São Paulo 13083-862, Brazil.
authors.forename: Leonardo R
authors.initials: LR
authors.lastname: Silveira
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam 3015 CE, The Netherlands.
authors.forename: Maikel P
authors.initials: MP
authors.lastname: Peppelenbosch
authors.affiliation: Department of Biochemistry and Tissue Biology, Biology Institute, University of Campinas, Campinas, São Paulo 13083-862, Brazil.
authors.forename: Carmen V
authors.initials: CV
authors.lastname: Ferreira-Halder
mesh_terms: D000208:Acute Disease; D019008:Drug Resistance, Neoplasm; D006019:Glycolysis; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D009363:Neoplasm Proteins; D017027:Protein Tyrosine Phosphatases
keywords: ACP1; CHEMORESISTANT LEUKEMIA CELLS; GLYCOLYTIC METABOLISM; KINOME; LMWPTP