ArticleRespiratory research2023
Inhibition of PKA/CREB1 pathway confers sensitivity to ferroptosis in non-small cell lung cancer.
Article in Respiratory research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- PRDX1 depletion predisposes to ferroptosis through inhibiting the cAMP pathway in B-cell acute lymphoblastic leukemia.Cancer gene therapy · 2026Article
- LncRNA FEZF1-AS1 promotes the tumorigenesis and suppresses ferroptosis in non-small cell lung cancer through the TNF-α/NF-κB pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- The DAG/PKC/CREB1/TGF-β1 axis drives shear-wave elastography stiffness and malignant progression in triple-negative breast cancer via lipid metabolic reprogramming.Cell death & disease · 2026Article
- Metabolic alterations and redox homeostasis in ferroptosis: emerging mechanisms and therapeutic implications.Archives of medical science : AMS · 2026Article
- Norepinephrine Induces Sertoli Cell Ferroptosis via Receptors Desensitization Causing Stress-Related Male Reproductive Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Hsa_circ_0026782 Acts as a "Molecular Break" of CREB1-Mediated Transcription by Promoting Its Phosphorylation at Ser142 That Prevents Keloid Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Ferroptosis in Cancer and Inflammatory Diseases: Mechanisms and Therapeutic Implications.MedComm · 2025Review
- SLC35F2 promotes the progression of NSCLC via regulating CREB1 expression.Cytotechnology · 2025Article
- Sarcosine sensitizes lung adenocarcinoma to chemotherapy by dual activation of ferroptosis via PDK4/PDHA1 signaling and NMDAR-mediated iron export.Experimental hematology & oncology · 2025Article
- Cytotoxic Effect of Escitalopram/Etoposide Combination on Etoposide-Resistant Lung Cancer.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Article
- Ferroptosis and Charcot-Marie-Tooth Disease 1A: Emerging Evidence for a Pathogenic Association.Antioxidants (Basel, Switzerland) · 2025Article
- HTB50-2 Inhibits Growth and Migration of Triple-negative Breast Cancer via FOSL2/FOXC1 Signaling Axis and Subsequent Ferroptosis.Current medicinal chemistry · 2025Article
- miR-30c-5p inhibits esophageal squamous cell carcinoma progression by repressing the PI3K/AKT signaling pathway.Thoracic cancer · 2024Article
- Identification of genetic associations between acute myocardial infarction and non-small cell lung cancer.Frontiers in molecular biosciences · 2024Article
- Targeting ferroptosis as a potential strategy to overcome the resistance of cisplatin in oral squamous cell carcinoma.Frontiers in pharmacology · 2024Review
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Ferroptosis is a type of regulated cell death characterized by iron accumulation and lipid peroxidation. The molecular mechanisms underlying ferroptosis regulation in non-small cell lung cancer (NSCLC) are poorly understood. In this study, we found that protein kinase A (PKA) inhibition enhanced ferroptosis susceptibility in NSCLC cells, as evidenced by reduced cell viability and increased lipid peroxidation. We further identified cAMP-responsive element protein 1 (CREB1), a transcription factor and a substrate of PKA, as a key regulator of ferroptosis. Knockdown of CREB1 sensitized NSCLC cells to ferroptosis inducers (FINs) and abolished the effects of PKA inhibitor and agonist, revealing the pivotal role of CREB1 in ferroptosis regulation. Using a high-throughput screening approach and subsequent validation by chromatin immunoprecipitation (ChIP) and dual-luciferase assays, we discovered that CREB1 transcriptionally activated stearoyl-CoA desaturase (SCD), an enzyme that catalyzes the conversion of saturated fatty acids to monounsaturated fatty acids. SCD conferred ferroptosis resistance by decreasing the availability of polyunsaturated fatty acids for lipid peroxidation, and its overexpression rescued the effect of CREB1 knockdown on ferroptosis in vitro. Besides, CREB1 knockdown suppressed xenograft tumor growth in the presence of Imidazole Ketone Erastin (IKE), a potent FIN, and this effect was reversed by SCD. Finally, we showed that high expression of CREB1 was associated with poor prognosis in NSCLC patients from public datasets and our institution. Collectively, this study illustrates the effect of PKA/CREB1/SCD axis in regulating ferroptosis of NSCLC, targeting this pathway may provide new strategies for treating NSCLC patients.
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Registered trials
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