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3-bromopyruvate as molecular tool to uncover the biological basis of protein phosphatase LMWPTP contribution to leukemic cells resistance

Grant number: 15/11433-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2015
Effective date (End): June 13, 2016
Field of knowledge:Biological Sciences - Biochemistry - Enzymology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Carmen Veríssima Ferreira
Grantee:Emanuella Maria Barreto Fonseca
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The great challenge of cancer therapy is to overcome the resistance to chemotherapy and metastasis. Therefore, a better understanding of these processes, the identification of molecular targets, and the development of new drugs with higher efficiency have been aimed of several research groups. In this scenario, our group initiated the investigation on the importance of the low molecular weight protein tyrosine phosphatase (LMWPTP) in 2005 and since then we showed that protein phosphatases inhibitors could be useful to increase the responsiveness of tumor cells to traditional chemotherapeutic. Then we established a collaboration with two groups from The Netherlands and it was possible to demonstrate that the LMWPTP contributes to: the maintenance of resistant phenotype and metastasis of solid tumors (prostate and rectal colon) and leukemia (myeloid leukemia human chronic). Besides, we observed that in samples from patients with prostate and colon cancer, the higher expression and activity of this enzyme correlate to the degree of aggressiveness, resistance and death of patients due to the tumor. Under the molecular aspect, until the moment, we demonstrate that the presence of LMWPTP ensures the activity of protein kinases related to survival and proliferation, and predominance of the glycolytic metabolism (glucose ’ lactate). Therefore, in this project we will focus on: 1) the inhibitory studies of LMWPTP by 3-bromopyruvate, an alkylating agent capable of causing great impact on the energy metabolism and consequently cell death; 2) the understanding of how this enzyme define the glucose metabolism fate in leukemia cells. Several tumor cells reprogram glucose metabolism in order to increase the synthesis of molecules that are crucial for the proliferation, resistance and adaptation to a hypoxic microenvironment. Therefore, with this project we intend to better understand how the LMWPTP contributes for leukemia resistance, to reinforce our hypothesis that this enzyme might be an interesting target and to demonstrate that part of the anti-tumor action of 3BP is due to inhibition of LMWPTP. (AU)

News published in Agência FAPESP Newsletter about the scholarship:
Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment 
Articles published in other media outlets (30 total):
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UOL: Enzima abundante em células tumorais poderá monitorar tratamento do câncer (11/Nov/2020)
Programa InfoSalud (Argentina): Científicos estudian la utilización de una enzima de las células tumorales para monitorear el cáncer (14/Jan/2021)
News Medical (Austrália): Researchers investigate protein phosphatase to identify new treatments for cancer, other diseases (13/Jan/2021)
Sound Health and Lasting Wealth (Nigéria): Researchers investigate protein phosphatase to identify new treatments for cancer, other diseases (13/Jan/2021)
Vectors Journal: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (13/Jan/2021)
Globe Health News: Researchers investigate protein phosphatase to identify new treatments for cancer, other diseases (13/Jan/2021)
Your Mag: Researchers investigate protein phosphatase to identify new treatments for cancer, other diseases (13/Jan/2021)
Medical Xpress (Reino Unido): Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Bioengineer (Reino Unido): Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Science Codex: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Life Extension Advocacy Foundation (EUA): Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Technology Networks (Reino Unido): Enzyme in Tumor Cells Could Be Used To Monitor Cancer Treatment (12/Jan/2021)
Scienmag Science Magazine (Reino Unido): Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Brightsurf: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
7thSpace: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Sciencenewsnet.in: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Amis-childrenshome: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
WorldNewsEra: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
The Uncover Reality: Scientists Study Use of Abundant Enzyme in Tumor Cells to Monitor Cancer Treatment (Medicine) (12/Jan/2021)
Your Mag: Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Love Avia for latest news and articles (EUA): Scientists study use of abundant enzyme in tumor cells to monitor cancer treatment (12/Jan/2021)
Pfarma: Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (26/Nov/2020)
Plantão News (MT): Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (15/Nov/2020)
NewsLab online: Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (13/Nov/2020)
UNICAMP - Universidade Estadual de Campinas: Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (11/Nov/2020)
LabNetwork: Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (11/Nov/2020)
Jornal Voz da Comunidade: Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (11/Nov/2020)
Tá Sabendo?: Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (11/Nov/2020)
ABIPTI - Associação Brasileira das Instituições de Pesquisa Tecnológica e Inovação: Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (11/Nov/2020)
Digital Rádio e TV: Cientistas avaliam usar enzima abundante em células tumorais para monitorar tratamento do câncer (11/Nov/2020)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PELIZZARO ROCHA-BRITO, KARIN JULIANE; BARRETO FONSECA, EMANUELLA MARIA; DE FREITAS OLIVEIRA, BRENO GERMANO; DE FATIMA, ANGELO; FERREIRA-HALDER, CARMEN VERISSIMA. Calix[6]arene diminishes receptor tyrosine kinase lifespan in pancreatic cancer cells and inhibits their migration and invasion efficiency. BIOORGANIC CHEMISTRY, v. 100, JUL 2020. Web of Science Citations: 0.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.