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ResearchIn-Press PreviewAngiogenesis
Open Access | 10.1172/JCI169671
1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
Find articles by Wang, T. in: JCI | PubMed | Google Scholar
1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
Find articles by Dong, Y. in: JCI | PubMed | Google Scholar
1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
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Huang, Z.
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1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
Find articles by Zhang, G. in: JCI | PubMed | Google Scholar
1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
Find articles by Zhao, Y. in: JCI | PubMed | Google Scholar
1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
Find articles by Yao, H. in: JCI | PubMed | Google Scholar
1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
Find articles by Hu, J. in: JCI | PubMed | Google Scholar
1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
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1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
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Cai, H.
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1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
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Liang, N.
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1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
Find articles by Xu, X. in: JCI | PubMed | Google Scholar
1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
Find articles by Yang, X. in: JCI | PubMed | Google Scholar
1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
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1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
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1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
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1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
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Strömblad, S.
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1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
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Qian, H.
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1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
Find articles by Jiang, C. in: JCI | PubMed | Google Scholar
1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
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1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden
2Department of General Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
3Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
4Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
5Department of Medicine, Karolinska Institutet, Stockholm, Sweden
6Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Physiology and Pathophysiology, Peking University, Beijing, China
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Bergo, M.
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Published August 31, 2023 - More info
Lung cancer progression relies on angiogenesis, which is a response to hypoxia typically coordinated by hypoxia-inducible transcription factors (HIFs); but growing evidence indicate that transcriptional programs beyond HIFs control tumor angiogenesis. Here we show that the redox-sensitive transcription factor BTB and CNC homology 1 (BACH1) controls the transcription of a broad range of angiogenesis genes. BACH1 is stabilized by lowering reactive oxygen species levels; consequently, angiogenesis gene expression in lung cancer cells, tumor organoids, and xenograft tumors increased substantially following vitamin C and E and N-acetylcysteine administration in a BACH1-dependent fashion under normoxia. Moreover, angiogenesis gene expression increased in endogenous BACH1–overexpressing cells and decreased in BACH1-knockouts in the absence of antioxidants. BACH1 levels also increased upon hypoxia and following administration of prolyl hydroxylase inhibitors in both HIF1a-knockout and wild-type cells. BACH1 was found to be a transcriptional target of HIF1α but BACH1’s ability to stimulate angiogenesis gene expression was HIF1a independent. Antioxidants increased tumor vascularity in vivo in a BACH1-dependent fashion, and overexpressing BACH1 rendered tumors sensitive to anti-angiogenesis therapy. BACH1 expression in tumor sections from lung cancer patients correlates with angiogenesis gene and protein expression. We conclude that BACH1 is an oxygen- and redox-sensitive angiogenesis transcription factor.