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A Novel Therapeutic Target, BACH1, Regulates Cancer Metabolism
Version 1
: Received: 28 January 2021 / Approved: 29 January 2021 / Online: 29 January 2021 (13:57:41 CET)
A peer-reviewed article of this Preprint also exists.
Padilla, J.; Lee, J. A Novel Therapeutic Target, BACH1, Regulates Cancer Metabolism. Cells 2021, 10, 634. Padilla, J.; Lee, J. A Novel Therapeutic Target, BACH1, Regulates Cancer Metabolism. Cells 2021, 10, 634.
Abstract
BTB domain and CNC homology 1 (BACH1) is a highly expressed transcription factor in tumors including breast and lung, relative to their non-tumor tissues. BACH1 is known to regulate multiple physiological processes including heme homeostasis, oxidative stress response, senescence, cell cycle, and mitosis. In a tumor, BACH1 promotes invasion and metastasis of cancer cells, and the expression of BACH1 presents a poor outcome for cancer patients including breast cancer patients. Recent studies identified novel functional roles of BACH1 in the regulation of metabolic pathways in cancer cells. BACH1 inhibits mitochondrial metabolism through transcriptional suppression of mitochondrial membrane genes. In addition, BACH1 suppresses activity of pyruvate dehydrogenase (PDH), a key enzyme that converts pyruvate to acetyl-CoA for the citric acid (TCA) cycle through transcriptional activation of pyruvate dehydrogenase kinase (PDK). Moreover, BACH1 increases glucose uptake and lactate secretion in aerobic glycolysis through the expression of metabolic enzymes involved such as hexokinase 2 (HK2) and glyceraldehyde 3- phosphate dehydrogenase (GAPDH). Pharmacological or genetic inhibition of BACH1 could reprogramme metabolic pathways, subsequently rendering metabolic vulnerability of cancer cells. Furthermore, inhibition of BACH1 decreased antioxidant-induced glycolysis rates as well as reduced migration and invasion of cancer cells, suggesting BACH1 as a potentially useful cancer therapeutic target.
Keywords
BTB and CNC homology 1 BACH1; mitochondrial metabolism; glycolysis; heme oxygenase 1 (HMOX1); mitochondrial electron transport chain (ETC); Nrf2 (encoded by Nfe2l2); metformin; hemin; breast cancer; lung cancer
Subject
Biology and Life Sciences, Anatomy and Physiology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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