Bonanomi Marcella, Salmistraro Noemi, Fiscon Giulia, Conte Federica, Paci Paola, Bravatà Valentina, Forte Giusi Irma, Volpari Tatiana, Scorza Manuela, Mastroianni Fabrizia, D'Errico Stefano, Avolio Elenio, Piccialli Gennaro, Colangelo Anna Maria, Vanoni Marco, Gaglio Daniela, Alberghina Lilia
ISBE. IT/Centre of Systems Biology, 20126 Milan, Italy.
Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy.
Cancers (Basel). 2021 Oct 9;13(20):5058. doi: 10.3390/cancers13205058.
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.
将葡萄糖代谢重编程为有氧糖酵解，可为癌细胞快速生成丙酮酸、ATP和NADH，而丙酮酸氧化为乳酸则确保氧化型NAD得以补充，以维持糖酵解。CtPB2是一种依赖NADH的转录共调节因子，有人提出它作为NADH传感器发挥作用，将代谢与表观遗传转录重编程联系起来。通过在一种三阴性人乳腺癌细胞系中整合代谢组学和转录组学，我们发现，CtBP2的基因下调和药理学下调通过调节氧化还原平衡、核苷酸合成、ROS生成和清除，强烈降低细胞增殖。我们的数据突出了NADH在控制癌基因依赖性代谢与表观遗传介导的转录程序之间的串扰中的关键作用，该转录程序维持癌细胞的能量和合成代谢需求。
