ArticleCell2019
Nrf2 Activation Promotes Lung Cancer Metastasis by Inhibiting the Degradation of Bach1.
Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 354 papers, 1 of them a synthesis that pooled it.
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Who cites it
354 citing papers in PubMed, 1 synthesis or guideline pooled it, 593 citations in OpenAlex.
- Rejuvenation of Bone Marrow Mesenchymal Stem Cells: Mechanisms and Their Application in Senile Osteoporosis Treatment.Biomolecules · 2025Pooled it
- Cysteine-based molecular switches: a focus on KEAP1 and BACH1 in regulating the antioxidant response.Archives of toxicology · 2026Review
- p-Coumaric acid inhibits hepatocellular carcinoma through promoting ROS accumulation.Medical oncology (Northwood, London, England) · 2026Article
- Boosting T cell antioxidant capacity: A strategic approach to overcome immunosuppression in solid tumors.Redox biology · 2026Review
- Heme as a versatile signaling molecule: Coordinating mitochondrial metabolism with global cellular responses.The Journal of biological chemistry · 2026Review
- SMARCA4, STK11, and KEAP1 co-inactivation associates with poor prognosis and upregulation of the TGF-β pathway in lung adenocarcinoma.Translational oncology · 2026Article
- A targetable ALDH3A2-NRF2 axis mediates KEAP1-mutant tumour development via ferroptosis inhibition.Cell death and differentiation · 2026Article
- HNF4α controls growth, identity, and KRAS inhibitor response in invasive mucinous adenocarcinoma of the lung.The Journal of clinical investigation · 2026Article
- LIF-Induced Tumor Plasticity Establishes an Immunosuppressive Myeloid Niche in LKB1-Mutant Lung Cancer.Cancer discovery · 2026Article
- Development of a high-throughput screening platform for identification of functional BACH1 inhibitors reveals compounds with anti-invasive potential.Redox biology · 2026Article
- Beyond KEAP1: The Context-Specific NRF2 Partner Code in Disease and Therapy.Antioxidants (Basel, Switzerland) · 2026Review
- Article
- BACH1 stabilization by antioxidants facilitates hepatocellular carcinoma metastasis.Cell death & disease · 2026Article
- Article
- Synergistic antioxidant and gene supplementation for high-efficacy retinitis pigmentosa therapy.Science advances · 2026Article
- Localized heme sensing through a ternary molecular glue.bioRxiv : the preprint server for biology · 2026Article
- Structural basis of NSD2 degradation via targeted recruitment of SCF-FBXO22.Nature communications · 2026Article
- Article
- A multi-omic approach reveals iron availability influences cell fate fidelity.npj metabolic health and disease · 2026Article
- Modulation of the Receptor Tyrosine Kinase TIE2/International journal of molecular sciences · 2026Article
294 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Approximately 30% of human lung cancers acquire mutations in either Keap1 or Nfe2l2, resulting in the stabilization of Nrf2, the Nfe2l2 gene product, which controls oxidative homeostasis. Here, we show that heme triggers the degradation of Bach1, a pro-metastatic transcription factor, by promoting its interaction with the ubiquitin ligase Fbxo22. Nrf2 accumulation in lung cancers causes the stabilization of Bach1 by inducing Ho1, the enzyme catabolizing heme. In mouse models of lung cancers, loss of Keap1 or Fbxo22 induces metastasis in a Bach1-dependent manner. Pharmacological inhibition of Ho1 suppresses metastasis in a Fbxo22-dependent manner. Human metastatic lung cancer display high levels of Ho1 and Bach1. Bach1 transcriptional signature is associated with poor survival and metastasis in lung cancer patients. We propose that Nrf2 activates a metastatic program by inhibiting the heme- and Fbxo22-mediated degradation of Bach1, and that Ho1 inhibitors represent an effective therapeutic strategy to prevent lung cancer metastasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.