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Hematogenous tumor metastasis in colon rectal cancer cells: influence of LMWPTP and 3-bromopyruvate

Grant number: 17/08119-8
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): December 01, 2017
Effective date (End): August 31, 2020
Field of knowledge:Biological Sciences - Biochemistry - Enzymology
Principal Investigator:Carmen Veríssima Ferreira
Grantee:Alessandra Valéria de Sousa Faria
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:15/20412-7 - Low molecular weight protein tyrosine phosphatase in colorectal cancer: from the bench to product generation, AP.TEM
Associated scholarship(s):18/00736-0 - MicroRNAs in stool and platelets biology from gastroenterology cancer patient samples that correlate with ACP1 protein tyrosine phosphatase: colorectal cancer screening, BE.EP.DR


Despite the great progress in the development of cancer treatment protocols, the effectiveness of the therapy of several tumors is still a challenge, especially in metastatic cases. Over the last decade, our research group has explored signal transduction pathways for the understanding of tumor biology. Our studies are focused on the mechanisms and identification of molecular targets envisaging the decrease of the aggressiveness and resistance of tumor cells. Low Molecular Weight Protein Phosphatase Phosphatase (LMWPTP) is one of the potential targets described by our group, and we describe it as an important protein involved in tumor chemotherapic resistance and metastatic processes, including rectal cancer (CRC). However, specifically in the case of the metastatic process, the role of this phosphatase still needs to be clarified. Thus, the present project aims to evaluate if LMWPTP contributes to the hematogenic dissemination of CRC cells, focusing on the first phase of this process, which requires the interaction of tumor cells with platelets. For this, CRC cell lines with different levels of LMWPTP expression will be employed and the influence of the culture medium derived from the cells on the platelet function will be analyzed. In addition, we will evaluate if the level of intracellular LMWPTP correlates with a greater capacity of CRC-platelets interaction. Since the ability of platelet aggregation can correlate with the metastatic potential of the tumor, we show that the 3BP decrease the platelet function collagen-induced at health patients' samples (data at rebuttal letter). And we will proceed to show 3BP inhibition of platelet function mechanism by a) evaluation of the 3BP effect at platelet aggregation by agonists, at aggregometer; b) investigation of 3BP signaling pathways' modulation at platelet function; c) investigation of platelet aggregation induced by CRC cells with different LMWPTP expression; d) evaluation of CRC hematogenous tumor metastasis inhibition by 3BP using strategies for coculture system between platelet and CRC cells, and signaling pathways modulated by this interaction. Beyond that, this project will promote innovation by evaluating the 3BP mechanism of action at platelet function and the CRC hematogenous tumor metastasis inhibition. Overall, identify the LMWPTP role at metastatic potential by investigation of the effective interaction between of CRC cells and platelets and the contribution of metabolic pathways related to this phenomenon.

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Scientific publications (8)
(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)
CORDEIRO, HELON GUIMARAES; DE SOUSA FARIA, ALESSANDRA VALERIA; FERREIRA-HALDER, CARMEN VERISSIMA. Vemurafenib downmodulates aggressiveness mediators of colorectal cancer (CRC): Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP), Protein Tyrosine Phosphatase 1B (PTP1B) and Transforming Growth Factor ss (TGF ss). Biological Chemistry, v. 401, n. 9, p. 1063-1069, . (17/08119-8, 15/20412-7)
FARIA, ALESSANDRA V. S.; ANDRADE, SHEILA S.; PEPPELENBOSCH, MAIKEL P.; FERREIRA-HALDER, CARMEN V.; FUHLER, GWENNY M.. Platelets in aging and cancer-{''}double-edged sword{''}. CANCER AND METASTASIS REVIEWS, v. 39, n. 4, SI, . (17/08119-8, 17/26317-1, 16/14459-3, 15/20412-7, 18/00736-0)
FARIA, ALESSANDRA V. S.; ANDRADE, SHEILA S.; PEPPELENBOSCH, MAIKEL P.; FERREIRA-HALDER, V, CARMEN; FUHLER, GWENNY M.. The role of phospho-tyrosine signaling in platelet biology and hemostasis. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1868, n. 3, . (15/20412-7, 17/26317-1, 17/08119-8, 16/14459-3, 18/00736-0)
FARIA, ALESSANDRA V. S.; CLERICI, STEFANO P.; DE SOUZA OLIVEIRA, PATRICIA F.; QUEIROZ, KARLA C. S.; PEPPELENBOSCH, MAIKEL P.; FERREIRA-HALDER, CARMEN V.. LMWPTP modulates the antioxidant response and autophagy process in human chronic myeloid leukemia cells. Molecular and Cellular Biochemistry, v. 466, n. 1-2, p. 83-89, . (18/03593-6, 17/08119-8, 15/20412-7)
FARIA, ALESSANDRA V. S.; FONSECA, EMANUELLA MARIA BARRETO; CORDEIRO, HELON GUIMARAES; CLERICI, STEFANO PIATTO; FERREIRA-HALDER, CARMEN VERISSIMA. Low molecular weight protein tyrosine phosphatase as signaling hub of cancer hallmarks. CELLULAR AND MOLECULAR LIFE SCIENCES, v. 78, n. 4, p. 1263-1273, . (17/08119-8, 15/11433-0, 18/03593-6)
FARIA, ALESSANDRA V. S.; YU, BINGTING; MOMMERSTEEG, MICHIEL; DE SOUZA-OLIVEIRA, PATRICIA F.; ANDRADE, SHEILA S.; SPAANDER, MANON C. W.; DE MAAT, MONIEK P. M.; PEPPELENBOSCH, MAIKEL P.; FERREIRA-HALDER, V, CARMEN; FUHLER, GWENNY M.. Platelet-dependent signaling and Low Molecular Weight Protein Tyrosine Phosphatase expression promote aggressive phenotypic changes in gastrointestinal cancer cells. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, v. 1868, n. 1, . (17/26317-1, 18/00736-0, 16/14459-3, 17/08119-8, 15/20412-7)
CLERICI, STEFANO PIATTO; DE SOUZA OLIVEIRA, PATRICIA FERNANDES; AKAGI, ERICA MIE; CORDEIRO, HELON GUIMARAES; AZEVEDO-MARTINS, JORDANA MARIA; DE SOUSA FARIA, ALESSANDRA VALERIA; FERREIRA-HALDER, CARMEN VERISSIMA. A comprehensive review on the role of protein tyrosine phosphatases in gastric cancer development and progression. Biological Chemistry, v. 402, n. 6, p. 663-674, . (17/08119-8, 17/16625-0, 15/20412-7, 18/03593-6)
FARIA, ALESSANDRA V. S.; ANDRADE, SHEILA S.; REIJM, AGNES N.; SPAANDER, MANON C. W.; DE MAAT, MONIEK P. M.; PEPPELENBOSCH, MAIKEL P.; FERREIRA-HALDER, V, CARMEN; FUHLER, GWENNY M.. Targeting Tyrosine Phosphatases by 3-Bromopyruvate Overcomes Hyperactivation of Platelets from Gastrointestinal Cancer Patients. JOURNAL OF CLINICAL MEDICINE, v. 8, n. 7, . (17/08119-8, 18/00736-0, 15/20412-7)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
FARIA, Alessandra Valéria de Sousa. Hematogenous tumor metastasis in colorectal cancer cells: influence of tyrosine phosphatases and 3-bromopyruvate. 2020. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.

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