Oncophosphosignaling Favors a Glycolytic Phenotype in Human Drug Resistant Leukemia
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.
|Keywords||ACP1, Chemoresistant leukemia cells, Glycolytic metabolism, Kinome, LMWPTP|
|Persistent URL||dx.doi.org/10.1002/jcb.26034, hdl.handle.net/1765/100049|
|Journal||Journal of Cellular Biochemistry|
Faria, A.V. (Alessandra V.S.), Tornatore, T.F. (Thaís F.), Milani, R, de Souza Queiroz, K.C, Sampaio, I.H. (Igor H.), Fonseca, E.M. (Emanuella M.B.), … Ferreira-Halder, C.V. (Carmen V.). (2017). Oncophosphosignaling Favors a Glycolytic Phenotype in Human Drug Resistant Leukemia. Journal of Cellular Biochemistry. doi:10.1002/jcb.26034