Portal de Periódicos da CAPES

Artigo Acesso aberto Produção Nacional Revisado por pares

BIBTEX RIS

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

2020; Elsevier BV; Volume: 178; Linguagem: Inglês

10.1016/j.bcp.2020.114104

1873-2968

Letícia S. Ferraz, Renata Torres da Costa, Claudia A. Costa, César Augusto João Ribeiro, Denise C. Arruda, Silvya Stuchi Maria–Engler, Tiago Rodrigues,

PI3K/AKT/mTOR signaling in cancer

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-RAFV600E-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.