ArticleInternational journal of cancer2018
Arsenic promotes the COX2/PGE2-SOX2 axis to increase the malignant stemness properties of urothelial cells.
Article in International journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Integrative Network Pharmacology and Molecular Docking-Based Validation of Berberine as a Therapeutic Agent in Arsenic-Induced Cardiotoxicity.Cardiovascular toxicology · 2026Article
- Article
- Overexpression of BMAL-1 is related to progression of urothelial carcinoma in arsenic exposure area.International urology and nephrology · 2025Article
- Lumbrokinase Extracted fromBiomolecules · 2024Article
- The UF-5000 Atyp.C parameter is an independent risk factor for bladder cancer.Scientific reports · 2024Article
- TROP-2, NECTIN-4 and predictive biomarkers in sarcomatoid and rhabdoid bladder urothelial carcinoma.Pathologica · 2024Article
- Potent molecular-targeted therapies for gastro-entero-pancreatic neuroendocrine carcinoma.Cancer metastasis reviews · 2023Review
- Pevonedistat Inhibits SOX2 Expression and Sphere Formation but Also Drives the Induction of Terminal Differentiation Markers and Apoptosis within Arsenite-Transformed Urothelial Cells.International journal of molecular sciences · 2023Article
- Nanoplastics and Arsenic Co-Exposures Exacerbate Oncogenic Biomarkers under an In Vitro Long-Term Exposure Scenario.International journal of molecular sciences · 2022Article
- Impact of SOX2 function and regulation on therapy resistance in bladder cancer.Frontiers in oncology · 2022Review
- Long-term arsenic exposure impairs differentiation in mouse embryonal stem cells.Journal of applied toxicology : JAT · 2021Article
- Effects of Aspirin on Myocardial Ischemia-Reperfusion Injury in Rats through STAT3 Signaling Pathway.BioMed research international · 2021Article
- Flurbiprofen suppresses the inflammation, proliferation, invasion and migration of colorectal cancer cells via COX2.Oncology letters · 2020Article
- The inhibitory effect of compound ChlA-F on human bladder cancer cell invasion can be attributed to its blockage of SOX2 protein.Cell death and differentiation · 2020Article
- Environmental exposures, stem cells, and cancer.Pharmacology & therapeutics · 2019Review
- Aspirin alleviates endothelial gap junction dysfunction through inhibition of NLRP3 inflammasome activation in LPS-induced vascular injury.Acta pharmaceutica Sinica. B · 2019Article
- CD24 regulates cancer stem cell (CSC)-like traits and a panel of CSC-related molecules serves as a non-invasive urinary biomarker for the detection of bladder cancer.British journal of cancer · 2018Article
- Arsenic Alters Exosome Quantity and Cargo to Mediate Stem Cell Recruitment Into a Cancer Stem Cell-Like Phenotype.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Chronic arsenic exposure is associated with the development of urothelial carcinoma of the bladder (UCB). To elucidate the contribution of arsenic exposure to urothelial cancer stem cell (CSC) generation, we established an in vitro stepwise malignant model transformed by chronically exposing human urothelial cells to arsenic. Using this model, we found that chronic arsenic exposure endows urothelial cells with malignant stemness properties including increased expression of stemness-related factors such as SOX2, sphere formation, self-renewal, invasion and chemoresistance. SOX2 was gradually and irreversibly overexpressed in line with acquired sphere-forming and self-renewal abilities. Following gene set enrichment analyses of arsenic-exposed and arsenic-unexposed cells, we found COX2 as an enriched gene for oncogenic signature. Mechanistically, arsenic-induced COX2/PGE2 increases SOX2 expression that eventually promotes malignant stem cell generation and repopulation. In urine samples from 90 subjects exposed to arsenic and 91 control subjects, we found a significant linear correlation between SOX2 and COX2 expression and the potential of SOX2 and COX2 expression as urinary markers to detect subjects exposed to arsenic. Furthermore, the combination marker yielded a high sensitivity for UCB detection in a separate cohort. Finally, our in vitro model exhibits basal-type molecular features and dual inhibition of EGFR and COX2 attenuated stem cell enrichment more efficiently than an EGFR inhibitor alone. In conclusion, the COX2/PGE2-SOX2 axis promotes arsenic-induced malignant stem cell transformation. In addition, our findings indicate the possible use of SOX2 and COX2 expression as urinary markers for the risk stratification and detection of UCB.
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