ArticleFrontiers in cell and developmental biology2022
The Apoptotic Resistance of BRCA1-Deficient Ovarian Cancer Cells is Mediated by cAMP.
Article in Frontiers in cell and developmental biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 11 citations in OpenAlex.
- Network toxicology and interpretable modeling identify nicotine-associated neuroendocrine targets and a three-gene prognostic signature in breast cancer.Translational cancer research · 2026Article
- NEK1 Promotes Ovarian Cancer Progression via p53 Suppression While Enhancing Sensitivity to Genotoxic Therapy.Current issues in molecular biology · 2026Article
- Application of Artificial Intelligence in Stem Cells and Gene Therapy for Gynecological Cancers.Current stem cell research & therapy · 2026Review
- Evaluation of Mismatch Repair (MMR) and Breast Cancer-1 (BRCA-1) Statuses in Epithelial Ovarian Cancer.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Cellular cAMP Content and Mitochondrial Profile Define Different Subtypes of Ovarian Cancer Cells.International journal of molecular sciences · 2025Article
- Identification and validation of a prognostic signature of mJournal of thoracic disease · 2025Article
- Targeted cancer therapy potential of quercetin-conjugated with folic acid-modified nanocrystalline cellulose nanoparticles: a study on AGS and A2780 cell lines.BMC biotechnology · 2025Article
- Correlation analysis of disulfidptosis-related gene signatures with clinical prognosis and immunotherapy response in sarcoma.Scientific reports · 2024Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Progress in the studies on the molecular mechanisms associated with multidrug resistance in cancers.Acta pharmaceutica Sinica. B · 2023Review
- cAMP-Dependent Signaling and Ovarian Cancer.Cells · 2022Review
- Targeting purine metabolism in ovarian cancer.Journal of ovarian research · 2022Review
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Authors and funding
7 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Breast cancer type 1 susceptibility protein (BRCA1) is essential for homologous recombination repair of DNA double-strand breaks. Loss of BRCA1 is lethal to embryos due to extreme genomic instability and the activation of p53-dependent apoptosis. However, the apoptosis is resisted in BRCA1-deficient cancer cells even though their p53 is proficient. In this study, by analysis of transcriptome data of ovarian cancer patients bearing BRCA1 defects in TCGA database, we found that cAMP signaling pathway was significantly activated. Experimentally, we found that BRCA1 deficiency caused an increased expression of ADRB1, a transmembrane receptor that can promote the generation of cAMP. The elevated cAMP not only inhibited DNA damage-induced apoptosis through abrogating p53 accumulation, but also suppressed the proliferation of cytotoxic T lymphocytes by enhancing the expression of immunosuppressive factors DKK1. Inhibition of ADRB1 effectively killed cancer cells by abolishing the apoptotic resistance. These findings uncover a novel mechanism of apoptotic resistance in BRCA1-deficient ovarian cancer cells and point to a potentially new strategy for treating BRCA1-mutated tumors.
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