Crosstalk between kinases, phosphatases and miRNAs in cancer

Abrantes, Julia Laura Fernandes; Tornatore, Thaís F.; Pelizzaro-Rocha, Karin Juliane; Jesus, Marcelo Bispo de; Cartaxo, Rodrigo; Milani, Renato; Ferreira-Halder, Carmen Veríssima

doi:10.1016/j.biochi.2014.09.011

Cited by 10 publications

(6 citation statements)

References 287 publications

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“…Recent evidence suggests that there is a tight regulation of phosphatase and kinase activity in cancer cells [ 4 - 6 ]. Protein phosphatase 2A (PP2A), one of the main serine-threonine phosphatases, maintains cell homoeostasis by counteracting most of the kinase-driven intracellular signaling pathways [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Overexpression of PP2A inhibitor SET oncoprotein is associated with tumor progression and poor prognosis in human non-small cell lung cancer

Líu

Wang

et al. 2015

Oncotarget

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SET oncoprotein is an endogenous inhibitor of protein phosphatase 2A (PP2A), and SET-mediated PP2A inhibition is an important regulatory mechanism for promoting cancer initiation and progression of several types of human leukemia disease. However, its potential relevance in solid tumors as non-small cell lung cancer (NSCLC) remains mostly unknown. In this study, we showed that SET was evidently overexpressed in human NSCLC cell lines and NSCLC tissues. Clinicopathologic analysis showed that SET expression was significantly correlated with clinical stage (p < 0.001), and lymph node metastasis (p < 0.05). Kaplan-Meier analysis revealed that patients with high SET expression had poorer overall survival rates than those with low SET expression. Moreover, knockdown of SET in NSCLC cells resulted in attenuated proliferative and invasive abilities. The biological effect of SET on proliferation and invasion was mediated by the inhibition of the PP2A, which in turn, activation of AKT and ERK, increased the expression of cyclin D1 and MMP9, and decreased the expression of p27. Furthermore, we observed that restoration of PP2A using SET antagonist FTY720 impaired proliferative and invasive potential in vitro, as well as inhibited tumor growth in vivo of NSCLC cells. Taken together, SET oncoprotein plays an important role in NSCLC progression, which could serve as a potential prognosis marker and a novel therapeutic target for NSCLC patients.

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Section: Introductionmentioning

confidence: 99%

Overexpression of PP2A inhibitor SET oncoprotein is associated with tumor progression and poor prognosis in human non-small cell lung cancer

Líu

Wang

et al. 2015

Oncotarget

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“…The biochemical aspects behind drug resistance are still far from being fully revealed. Since, metabolic pathways depend on a tightly controlled balance between phosphorylation and dephosphorylation of proteins, kinases, and phosphatases have a key function in the cancer resistance process [Abrantes et al, ]. An earlier report from our group has shown a significant association of LMWPTP activity to chemoresistance of leukemia cells [Ferreira et al, ], which was partly due to the maintenance of Src and Bcr‐Abl activation.…”

Section: Discussionmentioning

confidence: 99%

Oncophosphosignaling Favors a Glycolytic Phenotype in Human Drug Resistant Leukemia

Faria

Tornatore

Milani

et al. 2017

J of Cellular Biochemistry

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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.

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“…As a consequence, genes demonstrating 3 0 UTR shortening show a loss of miRNA targeting while genes demonstrating an elongated 3 0 UTR show increased miRNA targeting. In human ASCs, differential APA usage in the 3 0 UTR of genes was associated with adipogenic differentiation and altered miRNA targeting [69]. The effects of 3 0 UTR shortening and altered miRNA targeting in adult muscle stem cells has also been demonstrated.…”

Section: Alterations In Mirna/mrna Targeting Through Changes In Mrnamentioning

confidence: 96%

MicroRNA regulation of stem cell differentiation and diseases of the bone and adipose tissue: Perspectives on miRNA biogenesis and cellular transcriptome

et al. 2016

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Crosstalk between kinases, phosphatases and miRNAs in cancer

Cited by 10 publications

References 287 publications

Overexpression of PP2A inhibitor SET oncoprotein is associated with tumor progression and poor prognosis in human non-small cell lung cancer

Overexpression of PP2A inhibitor SET oncoprotein is associated with tumor progression and poor prognosis in human non-small cell lung cancer

Oncophosphosignaling Favors a Glycolytic Phenotype in Human Drug Resistant Leukemia

MicroRNA regulation of stem cell differentiation and diseases of the bone and adipose tissue: Perspectives on miRNA biogenesis and cellular transcriptome

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