ArticlePloS one2015
Fractionated Ionizing Radiation Promotes Epithelial-Mesenchymal Transition in Human Esophageal Cancer Cells through PTEN Deficiency-Mediated Akt Activation.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Radiotherapy, EMP and dormancy in TME: An integrated perspective on tumor microenvironments and long-term relapse.iScience · 2026Review
- Nitroxoline Enhances Radiosensitivity in Non-Small Cell Lung Cancer by Suppressing STAT3-AKT-MTOR Survival Signaling.International journal of molecular sciences · 2026Article
- Molecular mechanism of non-coding RNAs-mediated radiosensitivity regulation in colorectal cancer.World journal of gastrointestinal oncology · 2025Review
- CRISPR/Cas9 system: a novel approach to overcome chemotherapy and radiotherapy resistance in cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Targeting radiotherapy-induced inflammation in cancer metastasis: insights into immune modulation, therapeutic opportunities and radiogenomics.Frontiers in oncology · 2025Review
- LncRNA PTENP1/miR-21/PTEN Axis Modulates EMT and Drug Resistance in Cancer: Dynamic Boolean Modeling for Cell Fates in DNA Damage Response.International journal of molecular sciences · 2024Article
- The linker of nucleoskeleton and cytoskeleton complex is required for X-ray-induced epithelial-mesenchymal transition.Journal of radiation research · 2023Article
- Identification of a three-gene prognostic signature for radioresistant esophageal squamous cell carcinoma.World journal of clinical oncology · 2023Article
- Roles of PTEN inactivation and PD-1/PD-L1 activation in esophageal squamous cell carcinoma.Molecular biology reports · 2022Review
- Molecular mechanisms of chemo- and radiotherapy resistance and the potential implications for cancer treatment.MedComm · 2021Review
- Focused ultrasound radiosensitizes human cancer cells by enhancement of DNA damage.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2021Article
- Radiation induces epithelial to mesenchymal transition via upregulation of PD-L1 in nasopharyngeal carcinoma cell.Translational cancer research · 2021Article
- microRNAs identified in prostate cancer: Correlative studies on response to ionizing radiation.Molecular cancer · 2020Review
- Silencing Snail Reverses Epithelial-Mesenchymal Transition and Increases Radiosensitivity in Hypopharyngeal Carcinoma.OncoTargets and therapy · 2020Article
- Depletion of MLKL inhibits invasion of radioresistant nasopharyngeal carcinoma cells by suppressing epithelial-mesenchymal transition.Annals of translational medicine · 2019Article
- Article
- Single-cell RNA-seq of esophageal squamous cell carcinoma cell line with fractionated irradiation reveals radioresistant gene expression patterns.BMC genomics · 2019Article
- Possible biomarkers for predicting lymph node metastasis of esophageal squamous cell carcinoma: a review.The Journal of international medical research · 2019Review
- PNUTS mediates ionizing radiation-induced CNE-2 nasopharyngeal carcinoma cell migration, invasion, and epithelial-mesenchymal transition via the PI3K/AKT signaling pathway.OncoTargets and therapy · 2019Article
- Melatonin receptor stimulation by agomelatine prevents Aβ-induced tau phosphorylation and oxidative damage in PC12 cells.Drug design, development and therapy · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In some esophageal cancer patients, radiotherapy may not prevent distant metastasis thus resulting in poor survival. The underlying mechanism of metastasis in these patients is not well established. In this study, we have demonstrated that ionizing radiation may induce epithelial-mesenchymal transition (EMT) accompanied with increased cell migration and invasion, through downregulation of phosphatase and tensin homolog (PTEN), and activation of Akt/GSK-3β/Snail signaling. We developed a radioresistant (RR) esophageal squamous cancer cell line, KYSE-150/RR, by fractionated ionizing radiation (IR) treatment, and confirmed its radioresistance using a clonogenic survival assay. We found that the KYSE-150/RR cell line displayed typical morphological and molecular characteristics of EMT. In comparison to the parental cells, KYSE-150/RR cells showed an increase in post-IR colony survival, migration, and invasiveness. Furthermore, a decrease in PTEN in KYSE-150/RR cells was observed. We postulated that over-expression of PTEN may induce mesenchymal-epithelial transition in KYSE-150/RR cells and restore IR-induced increase of cell migration. Mechanistically, fractionated IR inhibits expression of PTEN, which leads to activation of Akt/GSK-3β signaling and is associated with the elevated levels of Snail protein, a transcription factor involved in EMT. Correspondingly, treatment with LY294002, a phosphatidylinositol-3-kinase inhibitor, mimicked PTEN overexpression effect in KYSE-150/RR cells, further suggesting a role for the Akt/GSK-3β/Snail signaling in effects mediated through PTEN. Together, these results strongly suggest that fractionated IR-mediated EMT in KYSE-150/RR cells is through PTEN-dependent pathways, highlighting a direct proinvasive effect of radiation treatment on tumor cells.
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