Mitochondrial transcription factor A (TFAM) shapes metabolic and invasion gene signatures in melanoma.
Mitochondrial transcription factor A (TFAM) shapes metabolic and invasion gene signatures in melanoma.
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DOI：
10.1038/s41598-018-31170-6
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发表时间：
2018-09-21
影响因子：
4.6
通讯作者：
Silva WA Jr
中科院分区：
文献类型：
--
作者：
Araujo LF;Siena ADD;Plaça JR;Brotto DB;Barros II;Muys BR;Biagi CAO Jr;Peronni KC;Sousa JF;Molfetta GA;West LC;West AP;Leopoldino AM;Espreafico EM;Silva WA Jr
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.
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影响因子：
6.6
作者：
Gentric G;Mieulet V;Mechta-Grigoriou F
通讯作者：
Mechta-Grigoriou F
影响因子：
7.7
作者：
Dong, Lan-Feng;Kovarova, Jaromira;Neuzil, Jiri
通讯作者：
Neuzil, Jiri
影响因子：
11.8
作者：
Hosios AM;Hecht VC;Danai LV;Johnson MO;Rathmell JC;Steinhauser ML;Manalis SR;Vander Heiden MG
通讯作者：
Vander Heiden MG
影响因子：
11.2
作者：
Dufies, Maeva;Giuliano, Sandy;Pages, Gilles
通讯作者：
Pages, Gilles
影响因子：
64.5
作者：
Cancer Genome Atlas Network
通讯作者：
Cancer Genome Atlas Network