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Transcriptomics analysis and redox-dependent metabolic rewiring in triple-negative breast cancer cells

ABSTRACT: Transcriptomics analysis and redox-dependent metabolic rewiring in triple-negative breast cancer cells

PROVIDER: PRJNA740282 | ENA |

REPOSITORIES: ENA

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Transcriptomics analysis and redox-dependent metabolic rewiring in triple-negative breast cancer cells

Project description:Glucose metabolism toward aerobic glycolysis provides cancer cells with a rapid generation of pyruvate, ATP, and NADH. CtPB2, an NADH-dependent transcriptional co-regulator, has been proposed to work as an NADH sensor, linking metabolism to transcriptional reprogramming. Here we described how the down-regulation of CtBP2 strongly reduces cell proliferation in triple negative breast cancer (BC) cell line, by modulating several intracellular pathways also through gene expression modification. Our data highlight the critical role of NADH in controlling energetic and anabolic demands in cancer cells.

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Transcriptomics and Metabolomics Integration Reveals Redox-Dependent Metabolic Rewiring in Breast Cancer Cells.

Project description:Rewiring glucose metabolism toward aerobic glycolysis provides cancer cells with a rapid generation of pyruvate, ATP, and NADH, while pyruvate oxidation to lactate guarantees refueling of oxidized NAD+ to sustain glycolysis. CtPB2, an NADH-dependent transcriptional co-regulator, has been proposed to work as an NADH sensor, linking metabolism to epigenetic transcriptional reprogramming. By integrating metabolomics and transcriptomics in a triple-negative human breast cancer cell line, we show that genetic and pharmacological down-regulation of CtBP2 strongly reduces cell proliferation by modulating the redox balance, nucleotide synthesis, ROS generation, and scavenging. Our data highlight the critical role of NADH in controlling the oncogene-dependent crosstalk between metabolism and the epigenetically mediated transcriptional program that sustains energetic and anabolic demands in cancer cells.

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