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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Targeting Tyrosine Phosphatases by 3-Bromopyruvate Overcomes Hyperactivation of Platelets from Gastrointestinal Cancer Patients

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Author(s):
Faria, Alessandra V. S. [1, 2] ; Andrade, Sheila S. [3] ; Reijm, Agnes N. [1] ; Spaander, Manon C. W. [1] ; de Maat, Moniek P. M. [4] ; Peppelenbosch, Maikel P. [1] ; Ferreira-Halder, V, Carmen ; Fuhler, Gwenny M. [1]
Total Authors: 8
Affiliation:
[1] Erasmus MC, Dept Gastroenterol & Hepatol, NL-3000 CA Rotterdam - Netherlands
[2] V, Univ Estadual Campinas, Dept Biochem & Tissue Biol, UNICAMP, BR-13083862 Campinas, SP - Brazil
[3] PlateInnove Biotechnol, BR-13414018 Piracicaba, SP - Brazil
[4] Erasmus MC, Dept Hematol, NL-3000 CA Rotterdam - Netherlands
Total Affiliations: 4
Document type: Journal article
Source: JOURNAL OF CLINICAL MEDICINE; v. 8, n. 7 JUL 2019.
Web of Science Citations: 0
Abstract

Venous thromboembolism (VTE) is one of the most common causes of cancer related mortality. It has been speculated that hypercoagulation in cancer patients is triggered by direct or indirect contact of platelets with tumor cells, however the underlying molecular mechanisms involved are currently unknown. Unraveling these mechanisms may provide potential avenues for preventing platelet-tumor cell aggregation. Here, we investigated the role of protein tyrosine phosphatases in the functionality of platelets in both healthy individuals and patients with gastrointestinal cancer, and determined their use as a target to inhibit platelet hyperactivity. This is the first study to demonstrate that platelet agonists selectively activate low molecular weight protein tyrosine phosphatase (LMWPTP) and PTP1B, resulting in activation of Src, a tyrosine kinase known to contribute to several platelet functions. Furthermore, we demonstrate that these phosphatases are a target for 3-bromopyruvate (3-BP), a lactic acid analog currently investigated for its use in the treatment of various metabolic tumors. Our data indicate that 3-BP reduces Src activity, platelet aggregation, expression of platelet activation makers and platelet-tumor cell interaction. Thus, in addition to its anti-carcinogenic effects, 3-BP may also be effective in preventing platelet-tumor cell aggregationin cancer patients and therefore may reduce cancer mortality by limiting VTE in patients. (AU)

FAPESP's process: 17/08119-8 - Hematogenous tumor metastasis in colon rectal cancer cells: influence of LMWPTP and 3-bromopyruvate
Grantee:Alessandra Valéria de Sousa Faria
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 18/00736-0 - MicroRNAs in stool and platelets biology from gastroenterology cancer patient samples that correlate with ACP1 protein tyrosine phosphatase: colorectal cancer screening
Grantee:Alessandra Valéria de Sousa Faria
Support Opportunities: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 15/20412-7 - Low molecular weight protein tyrosine phosphatase in colorectal cancer: from the bench to product generation
Grantee:Carmen Veríssima Ferreira
Support Opportunities: Research Projects - Thematic Grants