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

Autor:	Araujo LF; Department of Genetics-Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; National institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell-based Therapy-CEPID/FAPESP, Ribeirão Preto, Brazil.; Medical Genomics Laboratory, CIPE, AC Camargo Cancer Center, São Paulo, Brazil., Siena ADD; Department of Genetics-Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; National institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell-based Therapy-CEPID/FAPESP, Ribeirão Preto, Brazil., Plaça JR; National institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell-based Therapy-CEPID/FAPESP, Ribeirão Preto, Brazil., Brotto DB; Department of Genetics-Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; National institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell-based Therapy-CEPID/FAPESP, Ribeirão Preto, Brazil., Barros II; Department of Genetics-Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; National institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell-based Therapy-CEPID/FAPESP, Ribeirão Preto, Brazil., Muys BR; Department of Genetics-Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; National institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell-based Therapy-CEPID/FAPESP, Ribeirão Preto, Brazil., Biagi CAO Jr; Department of Genetics-Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; National institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell-based Therapy-CEPID/FAPESP, Ribeirão Preto, Brazil., Peronni KC; National institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell-based Therapy-CEPID/FAPESP, Ribeirão Preto, Brazil., Sousa JF; Department of Genetics-Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; National institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell-based Therapy-CEPID/FAPESP, Ribeirão Preto, Brazil., Molfetta GA; Department of Genetics-Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; National institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell-based Therapy-CEPID/FAPESP, Ribeirão Preto, Brazil., West LC; Microbial Pathogenesis & Immunology, Health Science Center, Texas A&M University, College Station, USA., West AP; Microbial Pathogenesis & Immunology, Health Science Center, Texas A&M University, College Station, USA., Leopoldino AM; Department of Clinical Analysis-Toxicology and Food Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil., Espreafico EM; Department of Cellular and Molecular Biology-Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Silva WA Jr; Department of Genetics-Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. wilsonjr@usp.br.; National institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell-based Therapy-CEPID/FAPESP, Ribeirão Preto, Brazil. wilsonjr@usp.br.; Center for Integrative System Biology-CISBi-NAP/USP, University of São Paulo, Ribeirão Preto, Brazil. wilsonjr@usp.br.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2018 Sep 21; Vol. 8 (1), pp. 14190. Date of Electronic Publication: 2018 Sep 21.
DOI:	10.1038/s41598-018-31170-6
Abstrakt:	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.
Databáze:	MEDLINE
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