ArticleRedox biology2018
DUOX2-mediated production of reactive oxygen species induces epithelial mesenchymal transition in 5-fluorouracil resistant human colon cancer cells.
Article in Redox biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Zn-Quer Nanozymes Reprogram the Malignant Phenotypic Transformation of Gastric Cancer Cells via Cascade Reactive Oxygen Species Coordination.ACS applied materials & interfaces · 2026Article
- Article
- HADHB mediates 5-fluorouracil sensitivity in colorectal cancer.Discover oncology · 2025Article
- Transcriptomic Landscape of Paclitaxel-Induced Multidrug Resistance in 3D Cultures of Colon Cancer Cell Line DLD1.International journal of molecular sciences · 2025Article
- IL-17A-producing NKp44(-) group 3 innate lymphoid cells accumulate in Familial Adenomatous Polyposis duodenal tissue.Nature communications · 2025Article
- NOX proteins and ROS generation: role in invadopodia formation and cancer cell invasion.Biological research · 2024Review
- Review
- Epigenetic regulation of DNA repair gene program by Hippo/YAP1-TET1 axis mediates sorafenib resistance in HCC.Cellular and molecular life sciences : CMLS · 2024Article
- The regulation of plasma gelsolin by DNA methylation in ovarian cancer chemo-resistance.Journal of ovarian research · 2024Article
- The Role of Cytokines in Activation of Tumour-promoting Pathways and Emergence of Cancer Drug Resistance.Current topics in medicinal chemistry · 2024Review
- Targeting proteasomal deubiquitinases USP14 and UCHL5 with b-AP15 reduces 5-fluorouracil resistance in colorectal cancer cells.Acta pharmacologica Sinica · 2023Article
- Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review.Cancers · 2023Review
- TRPV1 inhibition overcomes cisplatin resistance by blocking autophagy-mediated hyperactivation of EGFR signaling pathway.Nature communications · 2023Article
- Targeting epigenetic regulators to overcome drug resistance in cancers.Signal transduction and targeted therapy · 2023Review
- Dual Oxidase 2 (DUOX2) as a Proteomic Biomarker for Predicting Treatment Response to Chemoradiation Therapy for Locally Advanced Rectal Cancer: Using High-Throughput Proteomic Analysis and Machine Learning Algorithm.International journal of molecular sciences · 2022Article
- Natural Compound Shikonin Induces Apoptosis and Attenuates Epithelial to Mesenchymal Transition in Radiation-Resistant Human Colon Cancer Cells.Biomolecules & therapeutics · 2022Article
- ROS Promote Hypoxia-Induced Keratinocyte Epithelial-Mesenchymal Transition by Inducing SOX2 Expression and Subsequent Activation of Wnt/Oxidative medicine and cellular longevity · 2022Article
- Macrophages play a role in inflammatory transformation of colorectal cancer.World journal of gastrointestinal oncology · 2021Review
- A truncated protein product of the germline variant of theCancer biology & medicine · 2021Article
- DUOX2 promotes the progression of colorectal cancer cells by regulating the AKT pathway and interacting with RPL3.Carcinogenesis · 2021Article
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Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The therapeutic benefits offered by 5-fluorouracil (5-FU) are limited because of the acquisition of drug resistance, the main cause of treatment failure and metastasis. The ability of the cancer cells to undergo epithelial-mesenchymal transition (EMT) contributes significantly to cancer metastatic potential and chemo-resistance. However, the underlying molecular mechanisms of 5-FU-resistance have remained elusive. Here, we show that reactive oxygen species (ROS), produced by dual oxidase 2 (DUOX2), promote 5-FU-induced EMT. First, we showed that 5-FU-resistant SNUC5 colon cancer cells (SNUC5/FUR cells) undergo EMT by analyzing the expression of EMT markers such as N-cadherin, vimentin and E-cadherin. In addition, we found that the resistant cells expressed higher levels of Snail, Slug, Twist and Zeb1, which are all critical EMT regulators and had enhanced migratory and invasive capabilities. Furthermore, SNUC5/FUR cells had increased level of DUOX2, resulting in increased ROS level. This effect was due to the enhanced binding of the ten eleven translocation 1 (TET1) demethylase to the DUOX2 promoter in the SNUC5/FUR cells. Importantly, silencing of TET1 reversed the effects of 5-FU on the cells. Finally, the antioxidant N-acetylcysteine attenuated the effects of 5-FU on EMT and metastasis. Our study demonstrates the existence of a TET1/DUOX2/ROS/EMT axis that could play a role in colon cancer chemo-resistance and the aggressiveness of this cancer.
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