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LMWPTP modulates the antioxidant response and autophagy process in human chronic myeloid leukemia cells

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Abstract

In the last decade, several reports highlight the importance of the low molecular weight protein tyrosine phosphatase (LMWPTP) in cancer aggressiveness and resistance. Specifically, in chronic myeloid leukemia, we have reported that high expression of the LMWPTP maintains Src and Bcr-Abl kinases in an activated status and the glucose metabolism is directed to lactate production and, in turn, favor the pentoses pathway (one of the key process for antioxidant and protective responses). In this present study, we investigated the possible correlation between the LMWPTP and autophagy. In resistant chronic myeloid leukemia cells, the antioxidant response is supported by the glycolytic metabolism and antioxidant enzymes such as SOD and catalase, both favored by the LMWPTP. Therefore, when the cells were challenged by hydrogen peroxide treatment, the LMWPTP level goes down as well as SOD, and in turn, autophagy process was stimulated. The findings presented here reveal a novel aspect by which LMWPTP cooperates for the resistance of CML towards stressor stimuli.

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Abbreviations

CML:

Chronic myeloid leukemia

LMWPTP:

Low molecular weight protein tyrosine phosphatase

ROS:

Reactive oxygen species

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Acknowledgements

The authors are grateful for the financial support provided during the research from Sao Paulo Research Foundation (FAPESP)—(Grants 2015/20412–7; 2017/08119–8; 2018/03593–6), Coordination for the Improvement of Higher Education Personnel (CAPES), National Council for Scientific and Technological Development (CNPq). The authors are grateful for the equipment support from Laboratório Multiusuário de Biologia Celular e Molecular, Institute of Biology, University of Campinas. We thank the staff of the Life Sciences Core Facility (LaCTAD) from University of Campinas (UNICAMP), for the Cell Biology analysis.

Funding

This work was supported by the Sao Paulo Research Foundation (FAPESP) under Grants 2017/08119-8 (AVSF), 2018/03593-6 (SPC), and 2015/20412-7 (CVFH); This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)-Finance Code 001.

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Authors and Affiliations

  1. Department of Biochemistry and Tissue Biology, University of Campinas, UNICAMP, Campinas, SP, Brazil

    Alessandra V. S. Faria, Stefano P. Clerici, Patricia F. de Souza Oliveira, Karla C. S. Queiroz & Carmen V. Ferreira-Halder

  2. Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands

    Alessandra V. S. Faria & Maikel P. Peppelenbosch

Authors
  1. Alessandra V. S. Faria
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  2. Stefano P. Clerici
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  3. Patricia F. de Souza Oliveira
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  4. Karla C. S. Queiroz
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  5. Maikel P. Peppelenbosch
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  6. Carmen V. Ferreira-Halder
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Contributions

The head group leader CVFH contributed for the article conceptualization; AVSF, SPC, PSFO, KCSQ, MPP, and CVFH were responsible to design the methodology; AVSF, SPC, PSFO, and KCSQ performed the research investigation; AVSF was responsible for the original writing; SPC, PSFO, KCSQ, and CVFH were responsible for reviewing and editing; MPP and CVFH supervised the work; and all authors read and approved the final manuscript.

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Correspondence to Carmen V. Ferreira-Halder.

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11010_2020_3690_MOESM1_ESM.tif

Supplementary file1 (TIF 62724 kb)—Supplemental figure 1. Histograms for Western blots represents estern blot from Figure 1 (A), Figure 2 (B) and Figure 3 (C,D). It was considered the housekeeping control for total proteins and the ratio between phosphorylated/total forms for phosphorylated proteins. Statistical analysis: Figure 1 (A), P<0.05 K562 vs. Lucena-1; Figure 2 (B), P<0.05 Lucena-1 shScramble vs. Lucena-1 shACP1 and for figure 3 (C,D), P<0.05 Control vs. H2O2 treatments.

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Faria, A.V.S., Clerici, S.P., de Souza Oliveira, P.F. et al. LMWPTP modulates the antioxidant response and autophagy process in human chronic myeloid leukemia cells. Mol Cell Biochem 466, 83–89 (2020). https://doi.org/10.1007/s11010-020-03690-1

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