UCP2 Overexpression Redirects Glucose into Anabolic Metabolic Pathways

Sreedhar, Annapoorna; Cassell, Teresa; Smith, Parker; Lu, Daiwei; Nam, Hyung Wook; Lane, Andrew N.; Zhao, Yunfeng

doi:10.1002/pmic.201800353

“…5 B). However, for the same tumors we also observed an increase in the expression of uncoupling enzymes, especially UCP2, which has been implicated in protecting tumors from excessive ROS 109 and was recently shown to enhance tumorigenesis by inducing metabolic reprogramming towards anabolism 110 . Other UCPs have been associated with various cellular phenomena, mostly thermoregulation (UCP1) and neurodegeneration (UCP4 and UCP5) 111 , but the real significance of these enzymes in tumorigenesis remains to be established.…”

Section: Resultssupporting

confidence: 51%

A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism

Sheraj

¹

,

Güray

²

,

Banerjee

³

2021

Sci Rep

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Recently, there has been a resurgence of interest in metabolic rewiring of tumors to identify clinically relevant genes. However, most of these studies have had either focused on individual tumors, or are too general, providing a broad outlook on overall changes. In this study, we have first curated an extensive list of genes encoding metabolic enzymes and metabolite transporters relevant to carbohydrate, fatty acid and amino acid oxidation and biosynthesis. Next, we have used publicly available transcriptomic data for 20 different tumor types from The Cancer Genome Atlas Network (TCGA) and focused on differential expression of these genes between tumor and adjacent normal tissue. Our study revealed major transcriptional alterations in genes that are involved in central metabolism. Most tumors exhibit upregulation in carbohydrate and amino acid transporters, increased glycolysis and pentose phosphate pathway, and decreased fatty acid and amino acid oxidation. On the other hand, the expression of genes of the tricarboxylic acid cycle, anaplerotic reactions and electron transport chain differed between tumors. Although most transcriptomic alterations were conserved across many tumor types suggesting the initiation of common regulatory programs, expression changes unique to specific tumors were also identified, which can provide gene expression fingerprints as potential biomarkers or drug targets. Our study also emphasizes the value of transcriptomic data in the deeper understanding of metabolic changes in diseases.

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“…A cluster of seven tumors showed a tendency for overexpression of certain components of the ETC, which may be interpreted as more active TCA since the same cancers had higher expression of TCA and anaplerotic enzymes (Figure 5B). However, for the same tumors we also observed an increase in the expression of uncoupling enzymes, especially UCP2, which has been implicated in protecting tumors from excessive ROS 109 and was recently shown to enhance tumorigenesis by inducing metabolic reprogramming towards anabolism 110 . Other UCPs have been associated with various cellular phenomena, mostly thermoregulation (UCP1) and neurodegeneration (UCP4 and UCP5) 111 , but the real signi cance of these enzymes in tumorigenesis remains to be established.…”

Section: Electron Transport Chainsupporting

confidence: 51%

A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism

Sheraj

¹

,

Güray

²

,

Banerjee

³

2021

Preprint

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Recently, there has been a resurgence of interest in metabolic rewiring of tumors to identify clinically relevant genes. However, most of these studies have had either focused on individual tumors, or are too general, providing a broad outlook on overall changes. In this study, we have first curated an extensive list of genes encoding metabolic enzymes and metabolite transporters relevant to carbohydrate, fatty acid and amino acid oxidation and biosynthesis. Next, we have used publicly available transcriptomic data for 20 different tumor types from The Cancer Genome Atlas Network (TCGA) and focused on differential expression of these genes between tumor and adjacent normal tissue. Our study revealed major transcriptional alterations in genes that are involved in central metabolism. Most tumors exhibit upregulation in carbohydrate and amino acid transporters, increased glycolysis and pentose phosphate pathway, and decreased fatty acid and amino acid oxidation. On the other hand, the expression of genes of the tricarboxylic acid cycle, anaplerotic reactions and electron transport chain differed between tumors. Although most transcriptomic alterations were conserved across many tumor types suggesting the initiation of common regulatory programs, expression changes unique to specific tumors were also identified, which can provide gene expression fingerprints as potential biomarkers or drug targets. Our study also emphasizes the value of transcriptomic data in the deeper understanding of metabolic changes in diseases.

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“…Thus, in addition to the fact that UCP2 has a different expression in different tissues, it has been implicated as an enhancer of endothelial cell resistance to oxidative stress (34). As well as having a role in metabolic reprogramming in skin epidermal cells (35). Taken together, these results reinforce the correlation between UCP2 and metastasis (36).…”

Section: Discussionmentioning

confidence: 60%

Isothermal Microcalorimetry of Tumor Cells: Enhanced Thermogenesis by Metastatic Cells

Lemos

¹

,

Oliveira

²

,

Martins

³

et al. 2019

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Tumor cells exhibit rewired metabolism. We carried out comparative analyses attempting to investigate whether metabolic reprograming could be measured by isothermal microcalorimetry. Intact metastatic cell lines of tongue cell carcinoma, human and murine melanoma, lung, and breast tumors consistently released more heat than nonmetastatic cells or cells displaying lower metastatic potential. In tongue squamous carcinoma cells mitochondrial enriched extract reproduced the heat release pattern of intact cells. Cytochalasin D, an actin filament inhibitor, and suppression of metastasis marker Melanoma associated gene 10 (MAGEA10) decreased heat release. Uncoupling protein 2 was highly expressed in metastatic cells, but not in non-metastatic cells. Carnitine palmitoyl transferase-1 inhibitor, Etomoxir strongly inhibited heat release by metastatic cells, thus linking lipid metabolism to thermogenesis. We propose that heat release may be a quantifiable trait of the metastatic process.

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UCP2 Overexpression Redirects Glucose into Anabolic Metabolic Pathways

Cited by 14 publications

References 36 publications

A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism

A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism

A pan-cancer transcriptomic study showing tumor specific alterations in central metabolism

Isothermal Microcalorimetry of Tumor Cells: Enhanced Thermogenesis by Metastatic Cells

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