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 deph...

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Bibliographic Details
Published in:Journal of cellular biochemistry 2017-11, Vol.118 (11), p.3846-3854
Main Authors: Faria, Alessandra V.S., Tornatore, Thaís F., Milani, Renato, Queiroz, Karla C.S., Sampaio, Igor H., Fonseca, Emanuella M.B., Rocha‐Brito, Karin J.P., Santos, Tamira O., Silveira, Leonardo R., Peppelenbosch, Maikel P., Ferreira‐Halder, Carmen V.
Format: Article
Language:English
Subjects:
Abl protein
ACP1
Acute Disease
Addictions
BCR protein
Cell death
CHEMORESISTANT LEUKEMIA CELLS
Dehydrogenase
Dehydrogenases
Dephosphorylation
Drug resistance
Drug Resistance, Neoplasm
Enzymes
Fusion protein
Glucose
Glucose transporter
Glycolysis
GLYCOLYTIC METABOLISM
Humans
K562 Cells
KINOME
L-Lactate dehydrogenase
Lactate dehydrogenase
Lactic acid
Leukemia
Leukemia - metabolism
Leukemia - pathology
LMWPTP
Metabolism
Mitochondria
Molecular weight
Neoplasm Proteins - metabolism
Oxidation resistance
Oxidative metabolism
Phosphatase
Phosphorylation
Post-translation
Protein folding
Protein Tyrosine Phosphatases - metabolism
Protein-tyrosine-phosphatase
Proteins
Pyruvic acid
Signal Transduction
siRNA
Succinate dehydrogenase
Tyrosine
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Summary: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. The metabolic reprogramming in which kinases and LMWPTP take part, gives survival advantages to leukemia cells towards death stimuli, once key metabolites are produced for tumor cells via accelerate glycolysis and truncated Krebs cycle.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.26034