ArticleCell death & disease2018
GADD45α sensitizes cervical cancer cells to radiotherapy via increasing cytoplasmic APE1 level.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- CHA-mediated split G-quadruplex assembly: a ratiometric AIE strategy for label-free detection of APE1.Analytical and bioanalytical chemistry · 2026Article
- The clinical application value of dynamic monitoring of HPV ctDNA in concurrent chemoradiotherapy for locally advanced cervical cancer.NPJ precision oncology · 2026Article
- Mitochondrial reprogramming in cervical cancer: crosstalk with tumor immunity, HPV oncogenic signaling, and therapeutic resistance.Frontiers in immunology · 2026Review
- METTL3 mediates m6A methylation modification of ULBP2 and affects the progression of cervical cancer.Hereditas · 2025Article
- Targeting APE1: Advancements in the Diagnosis and Treatment of Tumors.Protein and peptide letters · 2025Review
- PXD101 inhibits malignant progression and radioresistance of glioblastoma by upregulating GADD45A.Journal of translational medicine · 2024Article
- Strategies, Challenges, and Prospects of Nanoparticles in Gynecological Malignancies.ACS omega · 2024Review
- Microbiome in radiotherapy: an emerging approach to enhance treatment efficacy and reduce tissue injury.Molecular medicine (Cambridge, Mass.) · 2024Review
- Revisiting Two Decades of Research Focused on Targeting APE1 for Cancer Therapy: The Pros and Cons.Cells · 2023Review
- DNA Damage Response in Cancer Therapy and Resistance: Challenges and Opportunities.International journal of molecular sciences · 2022Review
- HSP90 promotes radioresistance of cervical cancer cells via reducing FBXO6-mediated CD147 polyubiquitination.Cancer science · 2022Article
- Sinapine Thiocyanate Inhibits the Proliferation and Mobility of Pancreatic Cancer Cells by Up-Regulating GADD45A.Journal of Cancer · 2022Article
- The DeltaN p63 Promotes EMT and Metastasis in Bladder Cancer by the PTEN/AKT Signalling Pathway.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Inhibition of APE1 Expression Enhances the Antitumor Activity of Olaparib in Triple-Negative Breast Cancer.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Nanoparticle-based applications for cervical cancer treatment in drug delivery, gene editing, and therapeutic cancer vaccines.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2021Review
- IL-11 mediates the Radioresistance of Cervical Cancer Cells via the PI3K/Akt Signaling Pathway.Journal of Cancer · 2021Article
- LncRNA-PANDAR regulates the progression of thyroid carcinoma by targeting miR-637/KLK4.Journal of Cancer · 2021Article
- Pan-Cancer Analysis of NOS3 Identifies Its Expression and Clinical Relevance in Gastric Cancer.Frontiers in oncology · 2021Article
- U three protein 14a (UTP14A) promotes tumour proliferation and metastasis via the PERK/eIF2a/GRP78 signalling pathway in oesophageal squamous cell carcinoma.Journal of Cancer · 2021Article
- The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease.Drug discovery today · 2021Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Radioresistance remains a major clinical challenge in cervical cancer therapy. However, the mechanism for the development of radioresistance in cervical cancer is unclear. Herein, we determined that growth arrest and DNA-damage-inducible protein 45α (GADD45α) is decreased in radioresistant cervical cancer compared to radiosensitive cancer both in vitro and in vivo. In addition, silencing GADD45α prevents cervical cancer cells from undergoing radiation-induced DNA damage, cell cycle arrest, and apoptosis. More importantly, our data show that the overexpression of GADD45α significantly enhances the radiosensitivity of radioresistant cervical cancer cells. These data show that GADD45α decreases the cytoplasmic distribution of APE1, thereby enhancing the radiosensitivity of cervical cancer cells. Furthermore, we show that GADD45α inhibits the production of nitric oxide (NO), a nuclear APE1 export stimulator, by suppressing both endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) in cervical cancer cells. In conclusion, our findings suggest that decreased GADD45α expression significantly contributes to the development of radioresistance and that ectopic expression of GADD45α sensitizes cervical cancer cells to radiotherapy. GADD45α inhibits the NO-regulated cytoplasmic localization of APE1 through inhibiting eNOS and iNOS, thereby enhancing the radiosensitivity of cervical cancer cells.
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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.