A Novel Therapeutic Strategy Targeting BACH1 for Triple-Negative Breast Cancer
[Technical Report, Annual Report]
University of Chicago
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Breast cancer is the second most cancer among women with a chance of 15 percent in their life time. The most aggressive and lethal subtype of breast cancer is triple negative breast cancer TNBC, as evidenced with higher rates of recurrence,metastasis, and therapy resistance. However, there is lack of approved targeted therapy for the patients with TNBC. The goal of my research is to provide a novel therapeutic regimen to give benefits to the patients with TNBC. My research accomplishment during the second year 2018-2019 is continued from the first year to 1 define how BACH1 regulates mitochondrial membrane genes for metabolism of breast cancer using silencing BACH1-target genes, 2 Established whether combination treatment using hemin and metformin is effective for breast cancer treatment in xenograft models. Mitochondrial membrane genes including COX15 and UQCRC1 are direct target of BACH1 in breast cancer cells, thus silencing COX15 or UQCRC1 in BACH1-depleted cancer cells restored metformin sensitivity. Molecular mechanisms beyond is through restored NAD levels as well as decreased mitochondrial respiration capacity indicated as oxygen consumption rate OCR using Seahorse analysis. Importantly, metabolic flow of 13C-labeled glucose or glutamine was higher for glycolysis in BACH1-enriched cells relative to BACH1-depleted cells.
- Medicine and Medical Research