Targeting mitochondria in melanoma: Interplay between MAPK signaling pathway and mitochondrial dynamics.

Autor: Ferraz LS; Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC), Santo André, SP, Brazil., Costa RTD; Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC), Santo André, SP, Brazil., Costa CAD; Centro Interdisciplinar de Investigação Bioquímica (CIIB), Universidade de Mogi das Cruzes (UMC), Mogi das Cruzes, SP, Brazil., Ribeiro CAJ; Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC), Santo André, SP, Brazil., Arruda DC; Núcleo Integrado de Biotecnologia (NIB), Universidade de Mogi das Cruzes (UMC), Mogi das Cruzes, SP, Brazil., Maria-Engler SS; Departmento de Análises Clínicas e Toxicológicas, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, São Paulo, SP, Brazil., Rodrigues T; Centro de Ciências Naturais e Humanas (CCNH), Universidade Federal do ABC (UFABC), Santo André, SP, Brazil. Electronic address: tiago.rodrigues@ufabc.edu.br.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2020 Aug; Vol. 178, pp. 114104. Date of Electronic Publication: 2020 Jun 17.
DOI: 10.1016/j.bcp.2020.114104
Abstrakt: Melanoma is a malignant proliferative disease originated in melanocytes, characterized by high metastatic activity and by the activation of oncogenes, such as B-RAF (40-60% of cases). Recent studies have shown that vemurafenib (a MAPK inhibitor) promoted disturbance of mitochondrial bioenergetics, although underlying mechanisms are not fully comprehended. Here we showed that MAPK inhibition by vemurafenib in B-RAF V600E -mutated human melanoma culminated in the inhibition of DRP1 phosphorylation, associated to a large mitochondrial network remodeling to the hyperfused phenotype, and increased oxidative phosphorylation capacity. Such alterations may be associated to melanoma resistance to vemurafenib, since the impairment of oxidative phosphorylation increased the vemurafenib cytotoxicity. These results point to the potential of mitochondrial dynamics as a targetable pathway in melanoma.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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