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

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Ferraz, Leticia Silva [1] ; da Costa, Renata Torres [1] ; da Costa, Claudia Alves [2] ; Joao Ribeiro, Cesar Augusto [1] ; Arruda, Denise Costa [3] ; Maria-Engler, Silvya Stuchi [4] ; Rodrigues, Tiago [1]
Total Authors: 7
[1] Univ Fed ABC UFABC, Ctr Ciencias Nat & Humanas CCNH, Santo Andre, SP - Brazil
[2] Univ Mogi Cruzes UMC, Ctr Interdisciplinar Invest Bioquim CIIB, Mogi Das Cruzes, SP - Brazil
[3] Univ Mogi Cruzes UMC, Nucleo Integrad Biotecnol NIB, Mogi Das Cruzes, SP - Brazil
[4] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Anal Clin & Toxicol, Sao Paulo, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: Biochemical Pharmacology; v. 178, AUG 2020.
Web of Science Citations: 0

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. (AU)

FAPESP's process: 18/11972-7 - Analysis of Protein Expression Regulated by the Brn-2 Transcription Factor in Cells treated with Peptides-Derived from POU Domain of Brn-2 and Determination of the Internalization and Cell Localization of this Peptide
Grantee:Denise Costa Arruda
Support Opportunities: Regular Research Grants
FAPESP's process: 18/25747-5 - Alterations of mitochondrial morphology and dynamics in cancer: understanding of tumor biology and prospecting new therapeutic targets
Grantee:Tiago Rodrigues
Support Opportunities: Regular Research Grants
FAPESP's process: 17/04926-6 - Melanoma and chemoresistance: in vitro and in silico models to exploit therapeutic targets
Grantee:Silvya Stuchi Maria-Engler
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 15/25541-0 - Investigation of the mechanisms of toxicity in methylmalonic academia - evaluation of cell bioenergetics, oxidative stress, signaling pathways and potential strategies of protection
Grantee:César Augusto João Ribeiro
Support Opportunities: Regular Research Grants