ArticleProceedings of the National Academy of Sciences of the United States of America2016
Breast cancer tumorigenicity is dependent on high expression levels of NAF-1 and the lability of its Fe-S clusters.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 82 citations in OpenAlex.
- Regulatory networks of iron sulfur cluster biology in cancer mechanisms and therapeutic perspectives.iScience · 2026Review
- Exploring CISD1 as a multifaceted biomarker in cancer: Implications for diagnosis, prognosis, and immunotherapeutic response.Genes & diseases · 2025Article
- CISD3/MiNT is required for complex I function, mitochondrial integrity, and skeletal muscle maintenance.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Micronutrient Status and Breast Cancer: A Narrative Review.International journal of molecular sciences · 2024Review
- Iron-sulfur protein odyssey: exploring their cluster functional versatility and challenging identification.Metallomics : integrated biometal science · 2024Review
- Inhibition of CISD2 enhances sensitivity to doxorubicin in diffuse large B-cell lymphoma by regulating ferroptosis and ferritinophagy.Frontiers in pharmacology · 2024Article
- A combination of a cell penetrating peptide and a protein translation inhibitor kills metastatic breast cancer cells.Cell death discovery · 2023Article
- The Intriguing mitoNEET: Functional and Spectroscopic Properties of a Unique [2Fe-2S] Cluster Coordination Geometry.Molecules (Basel, Switzerland) · 2022Review
- The Cluster Transfer Function of AtNEET Supports the Ferredoxin-Thioredoxin Network of Plant Cells.Antioxidants (Basel, Switzerland) · 2022Article
- A peptide-derived strategy for specifically targeting the mitochondria and ER of cancer cells: a new approach in fighting cancer.Chemical science · 2022Article
- An anti-diabetic drug targets NEET (CISD) proteins through destabilization of their [2Fe-2S] clusters.Communications biology · 2022Article
- Anti-Inflammatory CDGSH Iron-Sulfur Domain 2: A Biomarker of Central Nervous System Insult in Cellular, Animal Models and Patients.Biomedicines · 2022Article
- A VDAC1-mediated NEET protein chain transfers [2Fe-2S] clusters between the mitochondria and the cytosol and impacts mitochondrial dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Multiple Poses and Thermodynamics of Ligands Targeting Protein Surfaces: The Case of Furosemide Binding to mitoNEET in Aqueous Solution.Frontiers in cell and developmental biology · 2022Article
- Iron-Sulfur Clusters: A Key Factor of Regulated Cell Death in Cancer.Oxidative medicine and cellular longevity · 2022Review
- A pathogenic role for histone H3 copper reductase activity in a yeast model of Friedreich's ataxia.Science advances · 2021Article
- Disrupting CISD2 function in cancer cells primarily impacts mitochondrial labile iron levels and triggers TXNIP expression.Free radical biology & medicine · 2021Article
- Mitochondrial iron-sulfur clusters: Structure, function, and an emerging role in vascular biology.Redox biology · 2021Review
- Sulfur Administration in Fe-S Cluster Homeostasis.Antioxidants (Basel, Switzerland) · 2021Review
- Iron-Sulfur Cluster Biogenesis as a Critical Target in Cancer.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
Iron-sulfur (Fe-S) proteins are thought to play an important role in cancer cells mediating redox reactions, DNA replication, and telomere maintenance. Nutrient-deprivation autophagy factor-1 (NAF-1) is a 2Fe-2S protein associated with the progression of multiple cancer types. It is unique among Fe-S proteins because of its 3Cys-1His cluster coordination structure that allows it to be relatively stable, as well as to transfer its clusters to apo-acceptor proteins. Here, we report that overexpression of NAF-1 in xenograft breast cancer tumors results in a dramatic augmentation in tumor size and aggressiveness and that NAF-1 overexpression enhances the tolerance of cancer cells to oxidative stress. Remarkably, overexpression of a NAF-1 mutant with a single point mutation that stabilizes the NAF-1 cluster, NAF-1(H114C), in xenograft breast cancer tumors results in a dramatic decrease in tumor size that is accompanied by enhanced mitochondrial iron and reactive oxygen accumulation and reduced cellular tolerance to oxidative stress. Furthermore, treating breast cancer cells with pioglitazone that stabilizes the 3Cys-1His cluster of NAF-1 results in a similar effect on mitochondrial iron and reactive oxygen species accumulation. Taken together, our findings point to a key role for the unique 3Cys-1His cluster of NAF-1 in promoting rapid tumor growth through cellular resistance to oxidative stress. Cluster transfer reactions mediated by the overexpressed NAF-1 protein are therefore critical for inducing oxidative stress tolerance in cancer cells, leading to rapid tumor growth, and drugs that stabilize the NAF-1 cluster could be used as part of a treatment strategy for cancers that display high NAF-1 expression.
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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.