ArticleMolecular carcinogenesis2018
Nickel exposure induces persistent mesenchymal phenotype in human lung epithelial cells through epigenetic activation of ZEB1.
Article in Molecular carcinogenesis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed, 61 citations in OpenAlex.
- Nickel exposure disrupts epigenetic repression of developmental genes in mouse embryonic stem cells.Toxicology and applied pharmacology · 2026Article
- TIP3;2 is a tonoplast transporter contributed to nickel detoxification in Arabidopsis thaliana.BMC plant biology · 2026Article
- Stage-Specific Reconstruction of Genome-Wide Genetic and Epigenetic Regulatory Networks Reveals Mechanistic Insights into Asthma Progression.International journal of molecular sciences · 2026Article
- Perspective on health and ecological risk assessments of potentially toxic metal(loid)s using aquatic biodiversity as biomonitoring indicators.Toxicology reports · 2025Review
- Safety Considerations of Trace Metals in Locally Produced Nutritive Food-Drinks Consumed in Yenagoa Metropolis, Nigeria.Biological trace element research · 2025Article
- Dysregulated bidirectional epithelial-mesenchymal crosstalk: a core determinant of lung fibrosis progression.Chinese medical journal pulmonary and critical care medicine · 2024Article
- Toxicological Aspects Associated with Consumption from Electronic Nicotine Delivery System (ENDS): Focus on Heavy Metals Exposure and Cancer Risk.International journal of molecular sciences · 2024Review
- Nickel-induced transcriptional memory in lung epithelial cells promotes interferon signaling upon nicotine exposure.Toxicology and applied pharmacology · 2023Article
- Quantification and Mapping of Alkylation in the Human Genome Reveal Single Nucleotide Resolution Precursors of Mutational Signatures.ACS central science · 2023Article
- Extracellular Vesicles as Mediators of Nickel-Induced Cancer Progression.International journal of molecular sciences · 2022Article
- MicroRNA-Gene Interactions Impacted by Toxic Metal(oid)s during EMT and Carcinogenesis.Cancers · 2022Review
- Review
- The Ni(II)-Binding Activity of the Intrinsically Disordered Region of Human NDRG1, a Protein Involved in Cancer Development.Biomolecules · 2022Article
- Toxic metals in the regulation of epithelial-mesenchymal plasticity: demons or angels?Cancer cell international · 2022Review
- Epigenetic Regulation in Exposome-Induced Tumorigenesis: Emerging Roles of ncRNAs.Biomolecules · 2022Review
- Identification of key genes and pathways between mild-moderate and severe asthmatics via bioinformatics analysis.Scientific reports · 2022Article
- Transcriptional repression of E-cadherin in nickel-exposed lung epithelial cells mediated by loss of Sp1 binding at the promoter.Molecular carcinogenesis · 2022Article
- Epithelial-mesenchymal transition: Insights into nickel-induced lung diseases.Seminars in cancer biology · 2021Review
- Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications.International journal of molecular sciences · 2021Review
- ZEB1: New advances in fibrosis and cancer.Molecular and cellular biochemistry · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Nickel (Ni) is an environmental and occupational carcinogen, and exposure to Ni is associated with lung and nasal cancers in humans. Furthermore, Ni exposure is implicated in several lung diseases including chronic inflammatory airway diseases, asthma, and fibrosis. However, the mutagenic potential of Ni is low and does not correlate with its potent toxicity and carcinogenicity. Therefore, mechanisms underlying Ni exposure-associated diseases remain poorly understood. Since the health risks of environmental exposures often continue post exposure, understanding the exposure effects that persist after the termination of exposure could provide mechanistic insights into diseases. By examining the persistent effects of Ni exposure, we report that Ni induces epithelial-mesenchymal transition (EMT) and that the mesenchymal phenotype remains irreversible even after the termination of exposure. Ni-induced EMT was dependent on the irreversible upregulation of ZEB1, an EMT master regulator, via resolution of its promoter bivalency. ZEB1, upon activation, downregulated its repressors as well as the cell-cell adhesion molecule, E-cadherin, resulting in the cells undergoing EMT and switching to persistent mesenchymal status. ZEB1 depletion in cells exposed to Ni attenuated Ni-induced EMT. Moreover, Ni exposure did not induce EMT in ZEB1-depleted cells. Activation of EMT, during which the epithelial cells lose cell-cell adhesion and become migratory and invasive, plays a major role in asthma, fibrosis, and cancer and metastasis, lung diseases associated with Ni exposure. Therefore, our finding of irreversible epigenetic activation of ZEB1 by Ni exposure and the acquisition of persistent mesenchymal phenotype would have important implications in understanding Ni-induced diseases.
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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.