Imatinib restores VASP activity and its interaction with Zyxin in BCR–ABL leukemic cells

Bernusso, Vanessa Aline; Machado-Neto, João Agostinho; Pericole, Fernando V; Vieira, Karla Priscila; Duarte, Adriana Silva Santos; Traina, Fabı́ola; Hansen, Marc D.H.; Saad, Sara Teresinha Olalla; Barcellos, Karin Spät Albino

doi:10.1016/j.bbamcr.2014.11.008

Cited by 16 publications

(17 citation statements)

References 41 publications

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“…Zyxin was also included in other models, demonstrating its importance for classifying ALL and AML, which is consistent with many studies (Crone et al, 2011;Bernusso et al, 2015;Tang et al, 2011;Hervy et al, 2010;Karimi and Farrokhnia, 2014;Joshi et al, 2016).…”

Section: Leukemia Datasupporting

confidence: 83%

High-dimensional Bayesian phenotype classification and model selection using genomic predictors

Panchal²

2019

Preprint

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Motivation:In this paper we describe a Bayesian hierarchical model termed 'PMMLogit' for classification and model selection in high-dimensional settings with binary phenotypes as outcomes. Posterior computation in the logistic model is known to be computationally demanding due to its non-conjugacy with common priors. We combine a Polya-Gamma based data augmentation strategy and use recent results on Markov chain Monte-Carlo (MCMC) techniques to develop an efficient and exact sampling strategy for the posterior computation. We use the resulting MCMC chain for model selection and choose the best combination(s) of genomic variables via posterior model probabilities. Further, a Bayesian model averaging (BMA) approach using the posterior mean, which averages across visited models, is shown to give superior prediction of phenotypes given genomic measurements. Results: Using simulation studies, we compared the performance of the proposed method with other popular methods. Simulation results show that the proposed method is quite effective in selecting the true model and has better estimation and prediction accuracy than other methods. These observations are consistent with theoretical results that have been developed in the statistics literature on optimality for this class of priors. Application to two well-known datasets on colon cancer and leukemia identified genes that have been previously reported in the clinical literature to be related to the disease outcomes. Availability: Source code is publicly available on GitHub at https://github.com/v-panchal/PMML.

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Section: Leukemia Datasupporting

confidence: 83%

High-dimensional Bayesian phenotype classification and model selection using genomic predictors

Panchal²

2019

Preprint

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“…In patients, an impaired LASP1-Y171 phosphorylation was seen under TKI therapy [11], but unfortunately, serine phosphorylation was not checked in that study. However, a recent publication showed imatinib-induced vasodilator-stimulated phosphoprotein (VASP) phosphorylation on S157 in K562 cells and in CML patients' bone marrow cells after imatinib treatment [51]. Completive data revealed a VASP-Y39 phosphorylation in BCR-ABL-positive leukemic cells [52].…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation-Dependent Differences in CXCR4-LASP1-AKT1 Interaction between Breast Cancer and Chronic Myeloid Leukemia

Butt

Stempfle

Lister

et al. 2020

Cells

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The serine/threonine protein kinase AKT1 is a downstream target of the chemokine receptor 4 (CXCR4), and both proteins play a central role in the modulation of diverse cellular processes, including proliferation and cell survival. While in chronic myeloid leukemia (CML) the CXCR4 is downregulated, thereby promoting the mobilization of progenitor cells into blood, the receptor is highly expressed in breast cancer cells, favoring the migratory capacity of these cells. Recently, the LIM and SH3 domain protein 1 (LASP1) has been described as a novel CXCR4 binding partner and as a promoter of the PI3K/AKT pathway. In this study, we uncovered a direct binding of LASP1, phosphorylated at S146, to both CXCR4 and AKT1, as shown by immunoprecipitation assays, pull-down experiments, and immunohistochemistry data. In contrast, phosphorylation of LASP1 at Y171 abrogated these interactions, suggesting that both LASP1 phospho-forms interact. Finally, findings demonstrating different phosphorylation patterns of LASP1 in breast cancer and chronic myeloid leukemia may have implications for CXCR4 function and tyrosine kinase inhibitor treatment.

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“…One of such functions is to regulate cell migration through VASP phosphorylation [ 22 , 35 ]. VASP is an actin binding phosphoprotein implicated in the control of actin cytoskeleton elongation and cell migration [ 36 – 39 ], whose phosphorylation at Ser239 impairs actin assembly [ 22 , 36 , 37 ]. Consistently, we observed that in MCL cells, acadesine triggered VASP phosphorylation at Ser239, as well as blockade of actin polymerization and migration in MCL cells.…”

Section: Discussionmentioning

confidence: 99%

Bcl-2highmantle cell lymphoma cells are sensitized to acadesine with ABT-199

et al. 2015

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Acadesine is a nucleoside analogue with known activity against B-cell malignancies. Herein, we showed that in mantle cell lymphoma (MCL) cells acadesine induced caspase-dependent apoptosis through turning on the mitochondrial apoptotic machinery. At the molecular level, the compound triggered the activation of the AMPK pathway, consequently modulating known downstream targets, such as mTOR and the cell motility-related vasodilator-stimulated phosphoprotein (VASP). VASP phosphorylation by acadesine was concomitant with a blockade of CXCL12-induced migration. The inhibition of the mTOR cascade by acadesine, committed MCL cells to enter in apoptosis by a translational downregulation of the antiapoptotic Mcl-1 protein. In contrast, Bcl-2 protein levels were unaffected by acadesine and MCL samples expressing high levels of Bcl-2 tended to have a reduced response to the drug. Targeting Bcl-2 with the selective BH3-mimetic agent ABT-199 sensitized Bcl-2 high MCL cells to acadesine. This effect was validated in vivo, where the combination of both agents displayed a more marked inhibition of tumor outgrowth than each drug alone. These findings support the notions that antiapoptotic proteins of the Bcl-2 family regulate MCL cell sensitivity to acadesine and that the combination of this agent with Bcl-2 inhibitors might be an interesting therapeutic option to treat MCL patients.

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Imatinib restores VASP activity and its interaction with Zyxin in BCR–ABL leukemic cells

Cited by 16 publications

References 41 publications

High-dimensional Bayesian phenotype classification and model selection using genomic predictors

High-dimensional Bayesian phenotype classification and model selection using genomic predictors

Phosphorylation-Dependent Differences in CXCR4-LASP1-AKT1 Interaction between Breast Cancer and Chronic Myeloid Leukemia

Bcl-2highmantle cell lymphoma cells are sensitized to acadesine with ABT-199

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