Autor segons l'article: McGrail K; Granado-Martínez P; Esteve-Puig R; García-Ortega S; Ding Y; Sánchez-Redondo S; Ferrer B; Hernandez-Losa J; Canals F; Manzano A; Navarro-Sabaté A; Bartrons R; Yanes O; Pérez-Alea M; Muñoz-Couselo E; Garcia-Patos V; Recio JA
Departament: Enginyeria Electrònica, Elèctrica i Automàtica
Autor/s de la URV: Yanes Torrado, Óscar
Paraules clau: Mutant melanoma tumors survival raf phosphorylation mutations kinase glucose cancer 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
Resum: NRAS-mutated melanoma lacks a specific line of treatment. Metabolic reprogramming is considered a novel target to control cancer; however, NRAS-oncogene contribution to this cancer hallmark is mostly unknown. Here, we show that NRASQ61-mutated melanomas specific metabolic settings mediate cell sensitivity to sorafenib upon metabolic stress. Mechanistically, these cells are dependent on glucose metabolism, in which glucose deprivation promotes a switch from CRAF to BRAF signaling. This scenario contributes to cell survival and sustains glucose metabolism through BRAF-mediated phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-2/3 (PFKFB2/PFKFB3). In turn, this favors the allosteric activation of phosphofructokinase-1 (PFK1), generating a feedback loop that couples glycolytic flux and the RAS signaling pathway. An in vivo treatment of NRASQ61 mutant melanomas, including patient-derived xenografts, with 2-deoxy-D-glucose (2-DG) and sorafenib effectively inhibits tumor growth. Thus, we provide evidence for NRAS-oncogene contributions to metabolic rewiring and a proof-of-principle for the treatment of NRASQ61-mutated melanoma combining metabolic stress (glycolysis inhibitors) and previously approved drugs, such as sorafenib.© 2022. The Author(s).
Àrees temàtiques: Zootecnia / recursos pesqueiros Saúde coletiva Química Psicología Planejamento urbano e regional / demografia Physics and astronomy (miscellaneous) Physics and astronomy (all) Odontología Nutrição Multidisciplinary sciences Multidisciplinary Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Matemática / probabilidade e estatística Interdisciplinar Geociências General physics and astronomy General medicine General chemistry General biochemistry,genetics and molecular biology Farmacia Engenharias iv Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência da computação Chemistry (miscellaneous) Chemistry (all) Biotecnología Biodiversidade Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all) Astronomia / física Antropologia / arqueologia
Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
Adreça de correu electrònic de l'autor: oscar.yanes@urv.cat
Identificador de l'autor: 0000-0003-3695-7157
Data d'alta del registre: 2024-09-07
Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
Enllaç font original: https://www.nature.com/articles/s41467-022-34907-0
URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
Referència a l'article segons font original: Nature Communications. 13 (1): 7113-7113
Referència de l'ítem segons les normes APA: McGrail K; Granado-Martínez P; Esteve-Puig R; García-Ortega S; Ding Y; Sánchez-Redondo S; Ferrer B; Hernandez-Losa J; Canals F; Manzano A; Navarro-Sab (2022). BRAF activation by metabolic stress promotes glycolysis sensitizing NRASQ61-mutated melanomas to targeted therapy. Nature Communications, 13(1), 7113-7113. DOI: 10.1038/s41467-022-34907-0
DOI de l'article: 10.1038/s41467-022-34907-0
Entitat: Universitat Rovira i Virgili
Any de publicació de la revista: 2022
Tipus de publicació: Journal Publications
Repositori URV