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The Interplay between Oxidative Phosphorylation and Glycolysis as a Potential Marker of Bladder Cancer Progression.

ABSTRACT: Urothelial bladder cancer (UBC) is the most common tumor of the urinary system. One of the biggest problems related to this disease is the lack of markers that can anticipate the progression of the cancer. Genomics and transcriptomics have greatly improved the prediction of risk of recurrence and progression. Further progress can be expected including information from other omics sciences such as metabolomics. In this study, we used 1H-NMR to characterize the intake of nutrients and the excretion of products in the extracellular medium of three UBC cell lines, which are representatives of low-grade tumors, RT4, high-grade, 5637, and a cell line that shares genotypic features with both, RT112. We have observed that RT4 cells show an activated oxidative phosphorylation, 5637 cells depend mostly on glycolysis to grow, while RT112 cells show a mixed metabolic state. Our results reveal the relative importance of glycolysis and oxidative phosphorylation in the growth and maintenance of different UBC cell lines, and the relationship with their genomic signatures. They suggest that cell lines associated with a low risk of progression present an activated oxidative metabolic state, while those associated with a high risk present a non-oxidative state and high glycolytic activity.

SUBMITTER: Petrella G

PROVIDER: S-EPMC7662640 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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The Interplay between Oxidative Phosphorylation and Glycolysis as a Potential Marker of Bladder Cancer Progression.

Petrella Greta G Ciufolini Giorgia G Vago Riccardo R Cicero Daniel Oscar DO

International journal of molecular sciences 20201030 21

Urothelial bladder cancer (UBC) is the most common tumor of the urinary system. One of the biggest problems related to this disease is the lack of markers that can anticipate the progression of the cancer. Genomics and transcriptomics have greatly improved the prediction of risk of recurrence and progression. Further progress can be expected including information from other omics sciences such as metabolomics. In this study, we used <sup>1</sup>H-NMR to characterize the intake of nutrients and t ...[more]

PMID: 33143087

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Project description:BackgroundThe predominant feature of cancer cells during the process of carcinogenesis is the inclination towards glycolytic metabolism rather than mitochondrial oxidative phosphorylation. Nevertheless, there is a scarcity of research investigating the correlation between bladder cancer and mitochondrial energy metabolism.MethodsA qPCR array comprising 90 genes associated with mitochondrial oxidative phosphorylation was employed to discern metabolic disparities between three sets of bladder cancer tissue and adjacent normal tissue. Wound healing and transwell assays were utilized to assess cell migration and invasion capabilities, respectively. Colony formation assays were conducted to ascertain the tumorigenic potential of the cells. The proliferative capacity of the cells was examined through in vitro CCK-8 assays. Additionally, nude mouse models were established to evaluate the impact of bladder tumor cells on in vivo proliferation. The Seahorse XFe96 Analyzer was utilized to quantify mitochondrial oxidative phosphorylation, while the levels of glucose-6-phosphate and pyruvate were assessed to evaluate glycolysis.ResultsExamination of qPCR array data demonstrated a noteworthy inhibition of mitochondrial oxidative phosphorylation in bladder cancer tissue, as evidenced by the down-regulation of a majority of genes associated with mitochondrial energy metabolism. Notably, GADD45B may potentially exert a significant influence on bladder cancer development, warranting further investigation. The down-regulation of GADD45B in bladder cancer cells resulted in impaired mitochondrial respiration and elevated levels of glycolysis, thereby enhancing cell migration and invasion. Conversely, up-regulation of GADD45B had the opposite effect. Furthermore, over-expression of GADD45B inhibited tumor proliferation and tumorigenesis in both in vitro and in vivo settings.ConclusionThese findings from our study indicate that the down-regulation of GADD45B promotes the shift of cell mitochondrial oxidative phosphorylation towards glycolysis, thereby facilitating the progression of bladder cancer.

Dataset Information

The Interplay between Oxidative Phosphorylation and Glycolysis as a Potential Marker of Bladder Cancer Progression.

Publications

The Interplay between Oxidative Phosphorylation and Glycolysis as a Potential Marker of Bladder Cancer Progression.

Similar Datasets

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