ArticleScientific reports2024
Dynamic phenotypic reprogramming and chemoresistance induced by lung fibroblasts in small cell lung cancer.
Article in Scientific reports, 2024. 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, 15 citations in OpenAlex.
- Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer.Annals of medicine · 2026Review
- Genes, fuel, and fate in lung cancer.Biochemical Society transactions · 2026Review
- IL-6/IL-6R-Mediated Mechanisms in Lung Cancer: From Pathogenesis to Potential Therapeutic Targets.Immunology · 2026Review
- Lung tumour secretome and extracellular vesicles: mechanisms, biomarkers, and therapeutic opportunities.Cancer metastasis reviews · 2026Review
- Mechanisms of resistance in small cell lung cancer.Chinese medical journal · 2026Review
- Cancer-Associated Fibroblasts Functions as Multifunctional Architects of the Tumor Stroma and Represent Emerging Therapeutic Vulnerabilities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Multi-omics reveals key molecular and cellular features of advanced small cell lung cancers associated with distinct therapeutic opportunities.Genome medicine · 2026Article
- Recent research advances in interleukin, microRNA and neuroendocrine tumor biomarkers (Review).Molecular and clinical oncology · 2025Review
- [Research Progress on the Role of Notch Signaling Pathway in Small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- A four gene risk score model for prognosis and immune microenvironment insights in small cell lung cancer based on CAF functional-related genes.Discover oncology · 2025Article
- Supinoxin blocks small cell lung cancer progression by inhibiting mitochondrial respiration through DDX5.iScience · 2025Article
- Current and future therapies for small cell lung carcinoma.Journal of hematology & oncology · 2025Review
- Cancer-Associated Fibroblasts as the "Architect" of the Lung Cancer Immune Microenvironment: Multidimensional Roles and Synergistic Regulation with Radiotherapy.International journal of molecular sciences · 2025Review
- Intratumoral heterogeneity and potential treatment strategies in small cell lung cancer.Frontiers in oncology · 2025Review
- Application Efficacy of Nursing Interventions Guided by the Medication-Psychological-Nursing-Family-Support (MPNFS) Framework in Mitigating Cancer-Related Fatigue and Enhancing Pulmonary Function Among Lung Cancer Patients Undergoing Chemotherapy.Cancer management and research · 2025Article
- Crosstalk between cancer-associated fibroblasts and non-neuroendocrine tumor cells in small cell lung cancer involves in glycolysis and antigen-presenting features.Molecular medicine (Cambridge, Mass.) · 2024Article
- [PKM1 Regulates the Expression of Autophagy and Neuroendocrine Markers in Small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2024Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Small cell lung cancer (SCLC) is heterogenous in phenotype and microenvironment. Dynamic phenotypic reprogramming, leading to heterogeneity, is prevalent in SCLC, while the mechanisms remain incompletely understood. Cancer-associated fibroblasts (CAFs) possess comprehensive roles in cancer progression, while their function in phenotypic reprogramming of SCLC remain elusive. Here, we obtained transcriptome data of SCLC tissues from publicly available databases, subsequently estimated abundance of CAFs. We found CAF-abundant SCLC exhibited non-neuroendocrine (Non-NE) characteristics. Supporting this, the positive correlation of expression level of α-SMA, the CAF marker, and expression level of REST, protein typically expressed in Non-NE type SCLC, was identified in SCLC tissue arrays. Moreover, we revealed that fibroblasts inhibited NE markers expression and cell proliferation of SCLC cells in the co-culture system comprising lung fibroblasts and SCLC cells, indicating a phenotypic reprogramming from NE to Non-NE. During this process, fibroblast-derived IL-6 activated the JAK2/STAT3 signaling, upregulated c-MYC expression, and subsequently activated the NOTCH pathway, driving phenotypic reprogramming. Moreover, CAF-enriched SCLC exhibited increased immune cell infiltration, elevated expression of immune activation-related signatures, and checkpoint molecules. Our data also highlighted the chemoresistance induced by fibroblasts in SCLC cells, which was effectively reversed by JAK inhibitor. In conclusion, fibroblasts induced phenotypic reprogramming of SCLC cells from NE to Non-NE, likely contributes to inflamed immune microenvironment and chemoresistance. These findings provide novel insights into the clinical implications of CAFs in SCLC.
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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.