Mitochondrial oxidative phosphorylation in cutaneous melanoma

Kumar, Prakrit R; Moore, Jamie A; Bowles, Kristian M.; Rushworth, Stuart A.; Moncrieff, Marc

doi:10.1038/s41416-020-01159-y

Cited by 43 publications

(47 citation statements)

References 112 publications

(222 reference statements)

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“…With the discovery of the concept of plasticity, this aspect of the Warburg hypothesis is challenged. There have been several instances of upregulated OXPHOS observed in multiple forms of cancer, such as melanoma [ 20 ], pancreatic ductal adenocarcinoma (PDAC) [ 21 ], leukemia, and subset of lymphomas [ 22 ].…”

Section: Glucose Metabolism and The Warburg Effect: A Century Latermentioning

confidence: 99%

Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation

Schiliro

Firestein

2021

Cells

286

152

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Cancer cells alter metabolic processes to sustain their characteristic uncontrolled growth and proliferation. These metabolic alterations include (1) a shift from oxidative phosphorylation to aerobic glycolysis to support the increased need for ATP, (2) increased glutaminolysis for NADPH regeneration, (3) altered flux through the pentose phosphate pathway and the tricarboxylic acid cycle for macromolecule generation, (4) increased lipid uptake, lipogenesis, and cholesterol synthesis, (5) upregulation of one-carbon metabolism for the production of ATP, NADH/NADPH, nucleotides, and glutathione, (6) altered amino acid metabolism, (7) metabolism-based regulation of apoptosis, and (8) the utilization of alternative substrates, such as lactate and acetate. Altered metabolic flux in cancer is controlled by tumor-host cell interactions, key oncogenes, tumor suppressors, and other regulatory molecules, including non-coding RNAs. Changes to metabolic pathways in cancer are dynamic, exhibit plasticity, and are often dependent on the type of tumor and the tumor microenvironment, leading in a shift of thought from the Warburg Effect and the “reverse Warburg Effect” to metabolic plasticity. Understanding the complex nature of altered flux through these multiple pathways in cancer cells can support the development of new therapies.

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Section: Glucose Metabolism and The Warburg Effect: A Century Latermentioning

confidence: 99%

Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation

Schiliro

Firestein

2021

Cells

286

152

View full text Add to dashboard Cite

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“…Oxidative phosphorylation and glycolysis have essential roles in malignant tumor cells. Metabolic phenotypes in melanoma also show some metabolic plasticity between glycolysis and oxidative phosphorylation [36]. To maintain their function and proliferation, melanoma cells typically transfer their metabolism from mitochondria to glycolytic ATP production.…”

Section: Risk Correlation Analysis In Vitro Validationmentioning

confidence: 99%

Gene Instability-Related lncRNA Prognostic Model of Melanoma Patients via Machine Learning Strategy

Yan

Wang

Shao

et al. 2021

Journal of Oncology

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Background. Melanoma is a common tumor characterized by a high mortality rate in its late stage. After metastasis, current treatment methods are relatively ineffective. Many studies have shown that long noncoding RNA (lncRNA) may participate in gene mutation and genomic instability in cancer. Methods. We downloaded transcriptome data, mutation data, and clinical follow-up data of melanoma patients from The Cancer Genome Atlas. We divided samples into groups according to the number of somatic cell mutations and then performed a differential analysis to screen out the differentially expressed genes. We then divided samples into genomic unstable and genomic stable groups. We compared lncRNA expression profiles in these groups and constructed a protein-coding genes network coexpressed with selected lncRNA to analyze the pathways enriched by these genes. Two machine learning methods, least absolute shrinkage and selector operation (LASSO) and support vector machine-recursive feature elimination (SVM-RFE), were applied to conduct the lncRNA-related prognostic model. Afterward, we performed survival analysis, risk correlation analysis, independent prognostic analysis, and clinical subgroup model validation. Finally, through wound healing assay and transwell assay, the function of AATBC was verified by A375 cell lines. Results. We screened 61 prognostic-related lncRNAs and constructed an lncRNA-mRNA coexpression network based on these lncRNAs. Seven lncRNAs were selected as common characteristic factors based on the two machine learning methods. The model formula was as follows: risk score = 0.085 ∗ AATBC + 0.190 ∗ AC026689.1−0.117 ∗ AC083799.1 + 0.036 ∗ AC091544.6−0.039 ∗ LINC01287−0.291 ∗ SPRY4.AS1 + 0.056 ∗ ZNF667.AS1. The seven lncRNAs in this formula are key candidates. Cell experiments have verified that knocking down AATBC in A375 cell lines can reduce the proliferation and invasion ability of melanoma cells. Conclusion. The lncRNA we identified provides a new way to study lncRNA’s role in the genomic instability of melanoma. Our findings may provide essential candidate biomarkers for the diagnosis and treatment of melanoma.

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“…This includes, for instance, higher proliferation of tumor stem cell populations, increased hypoxia, elevated M2 macrophage polarization, lower intratumoral T cell activation, additional NADPH for ROS detoxification, and metastasis via MMP production. An in-depth analysis of adaptive redox homeostasis in melanoma and energy metabolism has been provided recently [ 115 , 116 ], and the reader is referred to these and complementing views on oxidative phosphorylation [ 117 ].…”

Section: Pleiotropic Roles Of Ros In Melanoma Biologymentioning

confidence: 99%

ROS Pleiotropy in Melanoma and Local Therapy with Physical Modalities

Sagwal

Bekeschus

2021

Oxidative Medicine and Cellular Longevity

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Metabolic energy production naturally generates unwanted products such as reactive oxygen species (ROS), causing oxidative damage. Oxidative damage has been linked to several pathologies, including diabetes, premature aging, neurodegenerative diseases, and cancer. ROS were therefore originally anticipated as an imperative evil, a product of an imperfect system. More recently, however, the role of ROS in signaling and tumor treatment is increasingly acknowledged. This review addresses the main types, sources, and pathways of ROS in melanoma by linking their pleiotropic roles in antioxidant and oxidant regulation, hypoxia, metabolism, and cell death. In addition, the implications of ROS in various physical therapy modalities targeting melanoma, such as radiotherapy, electrochemotherapy, hyperthermia, photodynamic therapy, and medical gas plasma, are also discussed. By including ROS in the main picture of melanoma skin cancer and as an integral part of cancer therapies, a greater understanding of melanoma cell biology is presented, which ultimately may elucidate additional clues on targeting therapy resistance of this most deadly form of skin cancer.

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Mitochondrial oxidative phosphorylation in cutaneous melanoma

Cited by 43 publications

References 112 publications

Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation

Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation

Gene Instability-Related lncRNA Prognostic Model of Melanoma Patients via Machine Learning Strategy

ROS Pleiotropy in Melanoma and Local Therapy with Physical Modalities

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