Enhanced OXPHOS, glutaminolysis and beta-oxidation constitute the metastatic phenotype of melanoma cells

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dc.contributor.author Rodrigues, Mariana F.
dc.contributor.author Obre, Emilie
dc.contributor.author de Melo, Fabiana H. M. [UNIFESP]
dc.contributor.author Santos, Gilson C., Jr.
dc.contributor.author Galina, Antonio
dc.contributor.author Jasiulionis, Miriam G. [UNIFESP]
dc.contributor.author Rossignol, Rodrigue
dc.contributor.author Rumjanek, Franklin D.
dc.contributor.author Amoedo, Nivea D.
dc.date.accessioned 2020-08-21T16:59:50Z
dc.date.available 2020-08-21T16:59:50Z
dc.date.issued 2016
dc.identifier http://dx.doi.org/10.1042/BJ20150645
dc.identifier.citation Biochemical Journal. London, v. 473, p. 703-715, 2016.
dc.identifier.issn 0264-6021
dc.identifier.uri https://repositorio.unifesp.br/handle/11600/57783
dc.description.abstract Tumours display different cell populations with distinct metabolic phenotypes. Thus, subpopulations can adjust to different environments, particularly with regard to oxygen and nutrient availability. Our results indicate that progression to metastasis requires mitochondrial function. Our research, centered on cell lines that display increasing degrees of malignancy, focused on metabolic events, especially those involving mitochondria, which could reveal which stages are mechanistically associated with metastasis. Melanocytes were subjected to several cycles of adhesion impairment, producing stable cell lines exhibiting phenotypes representing a progression from non-tumorigenic to metastatic cells. Metastatic cells (4C11+) released the highest amounts of lactate, part of which was derived from glutamine catabolism. The 4C11+ cells also displayed an increased oxidative metabolism, accompanied by enhanced rates of oxygen consumption coupled to ATP synthesis. Enhanced mitochondrial function could not be explained by an increase in mitochondrial content or mitochondrial biogenesis. Furthermore, 4C11+ cells had a higher ATP content, and increased succinate oxidation (complex II activity) and fatty acid oxidation. In addition, 4C11+ cells exhibited a 2-fold increase in mitochondrial membrane potential (Lambda psi(mit])). Consistently, functional assays showed that the migration of cells depended on glutaminase activity. Metabolomic analysis revealed that 4C11+ cells could be grouped as a subpopulation with a profile that was quite distinct from the other cells investigated in the present study. The results presented here have centred on how the multiple metabolic inputs of tumour cells may converge to compose the so-called metastatic phenotype. en
dc.description.sponsorship CAPES-COFECUB
dc.description.sponsorship CNPq
dc.description.sponsorship FAPERJ
dc.description.sponsorship FAF
dc.description.sponsorship INCT/CNPq-Cancer
dc.format.extent 703-715
dc.language.iso eng
dc.publisher Portland Press Ltd
dc.relation.ispartof Biochemical Journal
dc.rights Acesso aberto
dc.subject energy metabolism en
dc.subject metastasis en
dc.subject mitochondrial physiology en
dc.subject OXPHOS en
dc.title Enhanced OXPHOS, glutaminolysis and beta-oxidation constitute the metastatic phenotype of melanoma cells en
dc.type Artigo
dc.description.affiliation Univ Fed Rio de Janeiro, Inst Bioquim Med Leopoldo De Meis, Rio De Janeiro, Brazil
dc.description.affiliation Univ Bordeaux Segalen, Malad Rares Genet & Metab, Bordeaux, France
dc.description.affiliation Univ Fed Sao Paulo, Dept Farmacol, Sao Paulo, Brazil
dc.description.affiliation Fac Ciencias Med Santa Casa Sao Paulo, Sao Paulo, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Dept Farmacol, Sao Paulo, Brazil
dc.description.sponsorshipID CAPES-COFECUB: 798-14
dc.description.sponsorshipID FAPERJ : -26/103.002/2011
dc.description.sponsorshipID FAPERJ: E26/102.231/2013
dc.identifier.doi 10.1042/BJ20150645
dc.description.source Web of Science
dc.identifier.wos WOS:000377208100005
dc.coverage London
dc.citation.volume 473


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