Advanced search
Start date
Betweenand

MCT1 as a target and response mediator in melanoma therapy

Grant number: 15/25351-6
Support type:Research Grants - Young Investigators Grants
Duration: May 01, 2016 - April 30, 2021
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Céline Marques Pinheiro
Grantee:Céline Marques Pinheiro
Home Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
Assoc. researchers:Adhemar Longatto Filho ; Daniel Onofre Vidal ; Débora Kristina Alves Fernandes ; Érica Aparecida de Oliveira ; FERNANDA FAIÃO FLORES ; Flavio Mavignier Cárcano ; Paula Comune Pennacchi ; Rui Manuel Vieira Reis ; Silvya Stuchi Maria-Engler ; Vinicius de Lima Vazquez
Associated scholarship(s):19/14189-4 - Effect of 3-bromopyruvate in melanoma cells resistant to vemurafenib, BP.MS
16/13021-4 - Sensitivity to 3-bromopyruvate and its relation to monocarboxylate 1 transporter (MCT-1) expression in primary melanoma cultures, BP.IC
16/10821-0 - MCT1 as a target and response mediator in melanoma therapy, BP.DD

Abstract

In the context of metabolic reprogramming of tumor cells (Warburg effect), several proteins show an increased expression, including monocarboxylate transporters (MCTs). Recently, MCT1 was identified as a major determinant of the sensitivity to 3-bromopyruvate (3-BP), one of the most promising inhibitors of glycolytic metabolism. So, in addition to a potential therapeutic target, MCT1 arises as a response mediator in cancer.Melanoma is the most aggressive form of skin cancer, and studies have shown that BRAF is one of the key oncogenes involved in melanoma tumorigenesis. Importantly, BRAF mutations induce the Warburg effect, and this reprogramming of energy metabolism has been identified as a possible strategy for treating melanoma.In this project, following the research that has been developed by the candidate in the last 10 years, the potential of MCT1 as a therapeutic target as well as a mediator of response to treatment with 3-BP as an antineoplastic agent for the treatment of melanoma will be evaluated by using diverse approaches, starting from the characterization of MCT1 expression in tumor samples, through a screening of melanoma cell lines sensitivity to 3-BP and association with MCT1 expression, and characterization of the effect of SLC16A1 (MCT1) knock-out, alone or combined with 3-BP treatment, in tumor aggressiveness characteristics. This project will be developed in close collaboration with researchers from different institutions and aims to open new perspectives for the development of more effective clinical trials in melanoma. (AU)

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)
PINHEIRO, CELINE; MIRANDA-GONCALVES, VERA; LONGATTO-FILHO, ADHEMAR; VICENTE, ANNA L. S. A.; BERARDINELLI, GUSTAVO N.; SCAPULATEMPO-NETO, CRISTOVAM; COSTA, RICARDO F. A.; VIANA, CRISTIANO R.; REIS, RUI M.; BALTAZAR, FATIMA; VAZQUEZ, VINICIUS L. The metabolic microenvironment of melanomas: Prognostic value of MCT1 and MCT4. CELL CYCLE, v. 15, n. 11, p. 1462-1470, 2016. Web of Science Citations: 14.

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