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.
Transcriptomics and metabolomics integration reveals redox-dependent metabolic rewiring in breast cancer cells / Bonanomi, M.; Salmistraro, N.; Fiscon, G.; Conte, F.; Paci, P.; Bravata, V.; Forte, G. I.; Volpari, T.; Scorza, M.; Mastroianni, F.; D'Errico, S.; Avolio, E.; Piccialli, G.; Colangelo, A. M.; Vanoni, M.; Gaglio, D.; Alberghina, L.. - In: CANCERS. - ISSN 2072-6694. - 13:20(2021). [10.3390/cancers13205058]
Transcriptomics and metabolomics integration reveals redox-dependent metabolic rewiring in breast cancer cells
Fiscon G.
;Paci P.
;Scorza M.
;D'errico S.;Avolio E.;Gaglio D.;
2021
Abstract
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.File | Dimensione | Formato | |
---|---|---|---|
Bonanomi_Transcriptomics_2021.pdf
accesso aperto
Note: https://doi.org/10.3390/cancers13205058
Tipologia:
Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza:
Creative commons
Dimensione
7.74 MB
Formato
Adobe PDF
|
7.74 MB | Adobe PDF |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.