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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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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.
Total Authors: 15
Affiliation:
[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
Total Affiliations: 8
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 8, SEP 21 2018.
Web of Science Citations: 1
Abstract

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)

FAPESP's process: 13/25119-0 - Energetic metabolism study on melanoma progression based on mitochondrial genome instability
Grantee:Luíza Ferreira de Araújo
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 09/53853-5 - Acquisition of a high-performance platform for computational analyses applied to the field of medicine
Grantee:Wilson Araújo da Silva Junior
Support type: Multi-user Equipment Program
FAPESP's process: 15/21940-7 - Examination of Mitochondrial DNA instability in melanoma tumorigenesis and metastasis
Grantee:Luíza Ferreira de Araújo
Support type: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 18/04017-9 - Genomic and functional characterization of putative melanoma-restricted lncRNAs (RMELs)
Grantee:Enilza Maria Espreafico
Support type: Regular Research Grants
FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
Grantee:Dimas Tadeu Covas
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC