ArticlePloS one2016
Smad2/3-Regulated Expression of DLX2 Is Associated with Radiation-Induced Epithelial-Mesenchymal Transition and Radioresistance of A549 and MDA-MB-231 Human Cancer Cell Lines.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- PTTG1-DLX2 axis drives malignant progression of lung adenocarcinoma by activating the WNT/β-catenin signaling pathway.Translational cancer research · 2026Article
- Epithelial-Mesenchymal Transition in Cancer: Insights Into Therapeutic Targets and Clinical Implications.MedComm · 2025Review
- GDF15 Contributes to Radioresistance by Mediating the EMT and Stemness of Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Ionizing Radiation Promotes Epithelial-Mesenchymal Transition Phenotype and Stem Cell Marker in The Lung adenocarcinoma: In Vitro and Bioinformatic Studiesc.Cell journal · 2022Article
- DLX2 Is a Potential Immune-Related Prognostic Indicator Associated with Remodeling of Tumor Microenvironment in Lung Squamous Cell Carcinoma: An Integrated Bioinformatical Analysis.Disease markers · 2022Article
- Metformin inhibits gastric cancer cell proliferation by regulation of a novel Loc100506691-CHAC1 axis.Molecular therapy oncolytics · 2021Article
- Activated ERK Signaling Is One of the Major Hub Signals Related to the Acquisition of Radiotherapy-Resistant MDA-MB-231 Breast Cancer Cells.International journal of molecular sciences · 2021Article
- Repeated Irradiation with γ-Ray Induces Cancer Stemness through TGF-β-DLX2 Signaling in the A549 Human Lung Cancer Cell Line.International journal of molecular sciences · 2021Article
- SMAD3 Host and Tumor Profiling to Identify Locally Advanced Rectal Cancer Patients at High Risk of Poor Response to Neoadjuvant Chemoradiotherapy.Frontiers in pharmacology · 2021Article
- Radiation induces epithelial to mesenchymal transition via upregulation of PD-L1 in nasopharyngeal carcinoma cell.Translational cancer research · 2021Article
- The protective effects of granulocyte-macrophage colony-stimulating factor against radiation-induced lung injury.Translational lung cancer research · 2020Article
- DNA Methylation and Breast Cancer Risk: An Epigenome-Wide Study of Normal Breast Tissue and Blood.Cancers · 2020Article
- Targeting hallmarks of cancer to enhance radiosensitivity in gastrointestinal cancers.Nature reviews. Gastroenterology & hepatology · 2020Review
- Dihydroartemisinin Prevents Distant Metastasis of Laryngeal Carcinoma by Inactivating STAT3 in Cancer Stem Cells.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Knockdown of SMAD3 inhibits the growth and enhances the radiosensitivity of lung adenocarcinoma via p21International journal of biological sciences · 2020Article
- Oncogenic Metabolism Acts as a Prerequisite Step for Induction of Cancer Metastasis and Cancer Stem Cell Phenotype.Oxidative medicine and cellular longevity · 2018Review
- Regulation of Tumor Progression by Programmed Necrosis.Oxidative medicine and cellular longevity · 2018Review
- Polydatin alleviated radiation-induced lung injury through activation of Sirt3 and inhibition of epithelial-mesenchymal transition.Journal of cellular and molecular medicine · 2017Article
- TGF-β-Dependent Growth Arrest and Cell Migration in Benign and Malignant Breast Epithelial Cells Are Antagonistically Controlled by Rac1 and Rac1b.International journal of molecular sciences · 2017Article
- IL-6/STAT3/TWIST inhibition reverses ionizing radiation-induced EMT and radioresistance in esophageal squamous carcinoma.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The control of radioresistance and metastatic potential of surviving cancer cells is important for improving cancer eradication by radiotheraphy. The distal-less homeobox2 (DLX2) gene encodes for a homeobox transcription factor involved in morphogenesis and its deregulation was found in human solid tumors and hematologic malignancies. Here we investigated the role of DLX2 in association with radiation-induced epithelial to mesenchymal transition (EMT) and stem cell-like properties and its regulation by Smad2/3 signaling in irradiated A549 and MDA-MB-231 human cancer cell lines. In irradiated A549 and MDA-MB-231 cells, EMT was induced as demonstrated by EMT marker expression, phosphorylation of Smad2/3, and migratory and invasive ability. Also, irradiated A549 and MDA-MB-231 cells showed increased cancer stem cells (CSCs) marker. Interestingly, DLX2 was overexpressed upon irradiation. Therefore, we examined the role of DLX2 in radiation-induced EMT and radioresistance. The overexpression of DLX2 alone induced EMT, migration and invasion, and CSC marker expression. The reduced colony-forming ability in irradiated cells was partially restored by DLX2 overexpression. On the other hand, the depletion of DLX2 using si-RNA abolished radiation-induced EMT, CSC marker expression, and phosphorylation of Smad2/3 in irradiated A549 and MDA-MB-231 cells. Also, depletion of DLX2 increased the radiation sensitivity in both cell lines. Moreover, knockdown of Smad2/3, a key activator of TGF-β1 pathway, abrogated the radiation-induced DLX2 expression, indicating that radiation-induced DLX2 expression is dependent on Smad2/3 signaling. These results demonstrated that DLX2 plays a crucial role in radioresistance, radiation-induced EMT and CSC marker expression, and the expression of DLX2 is regulated by Smad2/3 signaling in A549 and MDA-MB-231 cell lines.
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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.