| Full text | |
| Author(s): Show less - |
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: | 3 |
| 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: | 18/04017-9 - Genomic and functional characterization of putative melanoma-restricted lncRNAs (RMELs) |
| Grantee: | Enilza Maria Espreafico |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 13/08135-2 - CTC - Center for Cell-Based Therapy |
| Grantee: | Dimas Tadeu Covas |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| 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 Opportunities: | 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 Opportunities: | Scholarships abroad - Research Internship - Doctorate |
| FAPESP's process: | 13/25119-0 - Energetic metabolism study on melanoma progression based on mitochondrial genome instability |
| Grantee: | Luíza Ferreira de Araújo |
| Support Opportunities: | Scholarships in Brazil - Doctorate |