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.

Bonanomi, M., Salmistraro, N., Fiscon, G., Conte, F., Paci, P., Bravata, V., et al. (2021). Transcriptomics and metabolomics integration reveals redox-dependent metabolic rewiring in breast cancer cells. CANCERS, 13(20) [10.3390/cancers13205058].

Transcriptomics and metabolomics integration reveals redox-dependent metabolic rewiring in breast cancer cells

Bonanomi M.;Volpari T.;Mastroianni F.;Colangelo A. M.;Vanoni M.;Gaglio D.
;
Alberghina L.
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.
Articolo in rivista - Articolo scientifico
Scientifica
Cancer metabolic rewiring; CtBP2; Epigenetics; Metabolomics integration; Transcriptomics;
English
Bonanomi, M., Salmistraro, N., Fiscon, G., Conte, F., Paci, P., Bravata, V., et al. (2021). Transcriptomics and metabolomics integration reveals redox-dependent metabolic rewiring in breast cancer cells. CANCERS, 13(20) [10.3390/cancers13205058].
Bonanomi, M; Salmistraro, N; Fiscon, G; Conte, F; Paci, P; Bravata, V; Forte, G; Volpari, T; Scorza, M; Mastroianni, F; D'Errico, S; Avolio, E; Piccialli, G; Colangelo, A; Vanoni, M; Gaglio, D; Alberghina, L
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/331862
Citazioni
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 4
Social impact