Mitochondrialmetabolismis an attractive target forcancertherapy1,2. Reprogramming metabolic pathways could improve the ability of metabolic inhibitors to suppress cancers with limited treatment options, such as triple-negativebreastcancer(TNBC)1,3. Here we show that BTB and CNC homology1 (BACH1)4, a haem-binding transcription factor that is increased in expression in tumours from patients with TNBC, targetsmitochondrialmetabolism.BACH1decreases glucose utilization in the tricarboxylic acid cycle and negatively regulates transcription of electron transport chain (ETC) genes.BACH1depletion by shRNA or degradation by hemin sensitizes cells to ETC inhibitors such as metformin5,6, suppressing growth of both cell line and patient-derived tumour xenografts. Expression of a haem-resistantBACH1mutant in cells that express a short hairpin RNA forBACH1rescues theBACH1phenotype and restores metformin resistance in hemin-treated cells and tumours7. Finally,BACH1gene expression inversely correlates with ETC gene expression in tumours from patients withbreastcancerand in other tumour types, which highlights the clinical relevance of our findings. This study demonstrates thatmitochondrialmetabolismcan be exploited bytargetingBACH1to sensitizebreastcancerand potentially other tumour tissues tomitochondrialinhibitors.
doi: 10.1038/s41586-019-1005-x. Epub 2019 Mar 6.
老药新用，二甲双胍联合血红素治疗三阴性乳腺癌！
