Silva Ferraz 2020 Biochem Pharmacol
|Silva Ferraz L, Torres da Costa R, Alves da Costa C, Augusto João Ribeiro C, Costa Arruda D, Stuchi Maria-Engler S, Rodrigues T (2020) Targeting mitochondria in melanoma: interplay between MAPK signaling pathway and mitochondrial dynamics . Biochem Pharmacol [Epub ahead of print].|
Abstract: 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.
• Keywords: B-RAF mutation, MAPK signaling. Melanoma. Mitochondrial Dynamics. Vemurafenib • Bioblast editor: Plangger M
Labels: MiParea: Respiration, Pharmacology;toxicology Pathology: Cancer
Organism: Human Tissue;cell: Endothelial;epithelial;mesothelial cell Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ET