Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism.

ABSTRACT: Mitochondrial metabolism is an attractive target for cancer therapy^1,2. Reprogramming metabolic pathways could improve the ability of metabolic inhibitors to suppress cancers with limited treatment options, such as triple-negative breast cancer (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, targets mitochondrial metabolism. BACH1 decreases glucose utilization in the tricarboxylic acid cycle and negatively regulates transcription of electron transport chain (ETC) genes. BACH1 depletion by shRNA or degradation by hemin sensitizes cells to ETC inhibitors such as metformin^5,6, suppressing growth of both cell line and patient-derived t

SUBMITTER: Lee J 

PROVIDER: S-EPMC6698916 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature