Mitochondrial transcription factor A (TFAM) shapes metabolic and invasion gene signatures in melanoma

Autor(es):Mostrar menos -

Araujo, L. F. ^{[1, 2, 3]} ; Siena, A. D. D. ^{[1, 2]} ; Placa, J. R. ^[2] ; Brotto, D. B. ^{[1, 2]} ; Barros, I. I. ^{[1, 2]} ; Muys, B. R. ^{[1, 2]} ; Biagi Jr, C. A. O. ; Peronni, K. C. ^[4] ; Sousa, J. F. ^{[4, 5]} ; Molfetta, G. A. ^{[4, 5]} ; West, L. C. ^[6] ; West, A. P. ^[6] ; Leopoldino, A. M. ^[7] ; Espreafico, E. M. ^[8] ; Silva Jr, W. A.

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Genet, Ribeirao Preto Med Sch, Ribeirao Preto - Brazil

^[2] FAPESP, Ctr Cell Based Therapy CEPID, Natl Inst Sci & Technol Stem Cell & Cell Therapy, Ribeirao Preto - Brazil

^[3] AC Camargo Canc Ctr, CIPE, Med Genom Lab, Sao Paulo - Brazil

^[4] Biagi Jr, Jr., C. A. O., FAPESP, Ctr Cell Based Therapy CEPID, Natl Inst Sci & Technol Stem Cell & Cell Therapy, Ribeirao Preto - Brazil

^[5] Biagi Jr, Jr., C. A. O., Univ Sao Paulo, Dept Genet, Ribeirao Preto Med Sch, Ribeirao Preto - Brazil

^[6] Texas A&M Univ, Hlth Sci Ctr, Microbial Pathogenesis & Immunol, College Stn, TX - USA

^[7] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto - Brazil

^[8] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cellular & Mol Biol, Ribeirao Preto - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 8, SEP 21 2018.
• Citações Web of Science: 3

Resumo

Mitochondria are central key players in cell metabolism, and mitochondrial DNA (mtDNA) instability has been linked to metabolic changes that contribute to tumorigenesis and to increased expression of pro-tumorigenic genes. Here, we use melanoma cell lines and metastatic melanoma tumors to evaluate the effect of mtDNA alterations and the expression of the mtDNA packaging factor, TFAM, on energetic metabolism and pro-tumorigenic nuclear gene expression changes. We report a positive correlation between mtDNA copy number, glucose consumption, and ATP production in melanoma cell lines. Gene expression analysis reveals a down-regulation of glycolytic enzymes in cell lines and an up-regulation of amino acid metabolism enzymes in melanoma tumors, suggesting that TFAM may shift melanoma fuel utilization from glycolysis towards amino acid metabolism, especially glutamine. Indeed, proliferation assays reveal that TFAM-down melanoma cell lines display a growth arrest in glutamine-free media, emphasizing that these cells rely more on glutamine metabolism than glycolysis. Finally, our data indicate that TFAM correlates to VEGF expression and may contribute to tumorigenesis by triggering a more invasive gene expression signature. Our findings contribute to the understanding of how TFAM affects melanoma cell metabolism, and they provide new insight into the mechanisms by which TFAM and mtDNA copy number influence melanoma tumorigenesis. (AU)

• Processo FAPESP: 18/04017-9 - Caracterização genômica e funcional de potenciais lncRNAs restritos a melanoma (RMELs)
• Beneficiário: Enilza Maria Espreafico
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/08135-2 - CTC - Centro de Terapia Celular
• Beneficiário: Dimas Tadeu Covas
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 09/53853-5 - Aquisição de uma plataforma de alta performance para análises computacionais aplicadas à medicina
• Beneficiário: Wilson Araújo da Silva Junior
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 15/21940-7 - Análise da instabilidade do genoma mitocondrial na tumorigênese e metástase do melanoma
• Beneficiário: Luíza Ferreira de Araújo
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 13/25119-0 - Estudo do metabolismo energético na progressão do melanoma com base na instabilidade do genoma mitocondrial
• Beneficiário: Luíza Ferreira de Araújo
• Modalidade de apoio: Bolsas no Brasil - Doutorado