In this study, we show that down-regulation of the expression of the CtBP NADH-dependent transcriptional co-regulators reduces cell proliferation in a breast cancer cell line more than in untransformed, immortalized breast cell lines, partially reverting the oncogene-dependent intertwined metabolic and transcriptional rewiring that sustains energetic and anabolic demands in breast cancer cells. Here, CTBP1 is linked to breast cancer.