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Regulatory mechanisms of heme regulatory protein BACH1: a potential therapeutic target for cancer

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Abstract

A limited number of overexpressed transcription factors are associated with cancer progression in many types of cancer. BTB and CNC homology 1 (BACH1) is the first mammalian heme-binding transcription factor that belongs to the basic region leucine zipper (bZIP) family and a member of CNC (cap ‘n’ collar). It forms heterodimers with the small musculoaponeurotic fibrosarcoma (MAF) proteins and stimulates or suppresses the expression of target genes under a very low intracellular heme concentration. It possesses a significant regulatory role in heme homeostasis, oxidative stress, cell cycle, apoptosis, angiogenesis, and cancer metastasis progression. This review discusses the current knowledge about how BACH1 regulates cancer metastasis in various types of cancer and other carcinogenic associated factors such as oxidative stress, cell cycle regulation, apoptosis, and angiogenesis. Overall, from the reported studies and outcomes, it could be realized that BACH1 is a potential pharmacological target for discovering new therapeutic anticancer drugs.

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Abbreviations

BACH1:

BTB and CNC homology 1

BTB:

Broad complex tramtrack bric-a-brac domain

POZ:

Poxvirus and zinc finger

bZIP:

Basic region leucine zipper

CNC:

Cap ‘n’ collar

MAF:

Musculoaponeurotic fibrosarcoma

TF:

Transcription factor

HeRM:

Heme responsive motif

CP:

Cysteine and proline

CLS:

Cytoplasmic localization signal

CRM1:

Chromosome region maintenance 1

MARE:

MAF recognition elements

SMC:

Smooth muscle cells

AMI:

Acute myocardial infarction

EOC:

Epithelial ovarian cancer

EMT:

Endothelial mesenchymal transaction

CRC:

Colorectal cancer

TNBC:

Triple negative breast cancer

OCR:

Oxygen consumption rate

ETC:

Electron transport chain

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Acknowledgements

The authors are thankful to DST FIST, UGC-SAP, and MHRD-RUSA PHASE- 2.0 for providing the infrastructure facility.

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Authors and Affiliations

  1. Department of Environmental Biotechnology, School of Environmental Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu, 620024, India

    Abirami Arunachalam, Dinesh Kumar Lakshmanan, Guna Ravichandran, Soumi Paul & Sivasudha Thilagar

  2. Petroleum and Chemical Engineering, Faculty of Engineering, Universiti Teknologi Brunei, Bandar Seri Begawan, BE1410, Brunei Darussalam

    Sivakumar Manickam

  3. Department (Pharmaceutical Technology), Faculty of Pharmacy, UCSI University, South Campus, Taman Connaught, 56000, Kuala Lumpur, Malaysia

    Palanirajan Vijayaraj Kumar

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  1. Abirami Arunachalam
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AA and ST contributed for conception, design, and drafting of the manuscript. DKL, GR, SP, and PV-data search and formal analysis. SM critically reviewed the manuscript and comprehensively edited the fnal submitted version. All authors have reviewed and validated the fnal version of the manuscript.

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Correspondence to Sivasudha Thilagar.

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Arunachalam, A., Lakshmanan, D.K., Ravichandran, G. et al. Regulatory mechanisms of heme regulatory protein BACH1: a potential therapeutic target for cancer. Med Oncol 38, 122 (2021). https://doi.org/10.1007/s12032-021-01573-z

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