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Cited by 579Cancer, Hypoxia, and MetabolismGenomics, phytochemicals, and oxidative stressRedox biology and oxidative stress

BACH1 Stabilization by Antioxidants Stimulates Lung Cancer Metastasis

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Wiel, Clotilde, Le Gal, Kristell, Ibrahim, Mohamed X., Jahangir, Chowdhury Arif, Kashif, Muhammad, Yao, Haidong, Ziegler, Dorian V., Xu, Xiufeng +6 more·2019·Cell
DOI 10.1016/j.cell.2019.06.005
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Abstract

For tumors to progress efficiently, cancer cells must overcome barriers of oxidative stress. Although dietary antioxidant supplementation or activation of endogenous antioxidants by NRF2 reduces oxidative stress and promotes early lung tumor progression, little is known about its effect on lung cancer metastasis. Here, we show that long-term supplementation with the antioxidants N-acetylcysteine and vitamin E promotes KRAS-driven lung cancer metastasis. The antioxidants stimulate metastasis by reducing levels of free heme and stabilizing the transcription factor BACH1. BACH1 activates transcription of Hexokinase 2 and Gapdh and increases glucose uptake, glycolysis rates, and lactate secretion, thereby stimulating glycolysis-dependent metastasis of mouse and human lung cancer cells. Targeting BACH1 normalized glycolysis and prevented antioxidant-induced metastasis, while increasing endogenous BACH1 expression stimulated glycolysis and promoted metastasis, also in the absence of antioxidants. We conclude that BACH1 stimulates glycolysis-dependent lung cancer metastasis and that BACH1 is activated under conditions of reduced oxidative stress.

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Crossref · 10.1016/j.cell.2019.06.005

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  • Antioxidants suppress levels of free heme and stabilize transcription factor BACH1, important in heme homeostasis, maintenance of cell cycle, ROS formation, and other processes.

    “The antioxidants were responsible for suppressing levels of free heme and stabilization of transcription factor BACH1, important in heme homeostasis, maintenance of cell cycle, ROS formation, and other processes.”

    From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Wiel et al. 2019

  • Long-term administration of antioxidants, vitamin E, and N-acetylcysteine promotes KRAS-mediated lung cancer metastasis.

    “In another work, long-term administration of antioxidants, vitamin E, and N-acetylcysteine has been shown to promote KRAS-mediated lung cancer metastasis (Wiel et al. 2019).”

    From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Wiel et al. 2019

  • BACH1 activates transcription factors involved in triggering glycolysis, playing an important role in tumor growth promotion, metastasis, and chemoresistance in mouse and human lung cancer cells.

    “Subsequently, BACH1 activates transcription factors involved in the triggering process of glycolysis playing an important role in tumor growth promotion, metastasis, and chemoresistance in mouse and human lung cancer cells.”

    From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Wiel et al. 2019

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Authors
Wiel, C., Le Gal, K., Ibrahim, M. X., Jahangir, C. A., Kashif, M., Yao, H., Ziegler, D. V., Xu, X., Ghosh, T., Mondal, T., Kanduri, C., Lindahl, P., Sayin, V. I., & Bergo, M. O.
Affiliations
  • Karolinska Institutet (SE)
  • University of Gothenburg (SE)
  • Wallenberg Centre for Molecular and Translational Medicine (SE)
Corresponding author
Sayin, Volkan I.
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2019-07
Volume
178
Issue
2
Pages
330-345.e22
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2019.06.005
OpenAlex
W2953979824
Cited by
579
References
72
Citations by year
2026: 49 · 2025: 84 · 2024: 85 · 2023: 102 · 2022: 79 · 2021: 91 · 2020: 70 · 2019: 18
FWCI
20.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Cancerfonden
  • Knut och Alice Wallenbergs Stiftelse
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
BACH1, lung cancer metastasis, antioxidants, N-acetylcysteine, vitamin E, oxidative stress, KRAS-driven lung cancer, free heme, glycolysis, glucose uptake, hexokinase 2, glyceraldehyde-3-phosphate dehydrogenase, lactate secretion, Nrf2
MeSH terms
Animals, Antioxidants, Cell Movement, Glycolysis, Heme, Hexokinase, Humans, Lung Neoplasms, Neoplasm Metastasis, Mice, SCID, Mice, Inbred NOD, Reactive Oxygen Species, Mice, Knockout, Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating), RNA Interference, RNA, Small Interfering, Basic-Leucine Zipper Transcription Factors, NF-E2-Related Factor 2, Mice, Kaplan-Meier Estimate

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