# A Novel Therapeutic Target, BACH1, Regulates Cancer Metabolism

## TL;DR

BACH1, a protein found in high levels in breast and lung tumors, controls cancer cell metabolism and could be a new target for cancer treatment.

## Contribution

This paper identifies BACH1 as a novel regulator of cancer metabolism through multiple metabolic pathways and its inhibition as a potential therapeutic strategy.

## Key findings

- BACH1 suppresses mitochondrial metabolism by inhibiting mitochondrial membrane genes and PDH activity.
- BACH1 promotes aerobic glycolysis by increasing glucose uptake and lactate secretion via HK2 and GAPDH.
- Inhibiting BACH1 reprograms cancer cell metabolism and reduces migration and invasion.

## Abstract

BTB domain and CNC homology 1 (BACH1) is a transcription factor that is highly expressed 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 and lung 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 through the expression of metabolic enzymes involved such as hexokinase 2 (HK2) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) for aerobic glycolysis. Pharmacological or genetic inhibition of BACH1 could reprogram by increasing mitochondrial metabolism, subsequently rendering metabolic vulnerability of cancer cells against mitochondrial respiratory inhibition. 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.