ArticleNature communications2025
Actin dysregulation induces neuroendocrine plasticity and immune evasion: a vulnerability of small cell lung cancer.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Cell plasticity in cancer and therapy resistance.Experimental & molecular medicine · 2026Review
- CRACD loss drives hypoxia-induced immune escape in gastric cancer.Nature communications · 2026Article
- XPO1-mediated TRIM21 nuclear export reprograms TREM2+ macrophage polarization by targeting IRF3 to augment anti-PD-1 efficacy in small cell lung cancer.Nature communications · 2026Article
- Spatiotemporal Transcriptomic Dissection Uncovers Age-Dependent Deceleration of Esophageal Cell Differentiation.bioRxiv : the preprint server for biology · 2026Article
- NFATc3 Enhances DREAM Complex-Driven Transactivation.bioRxiv : the preprint server for biology · 2026Article
- Single-Cell Lineage Trajectory Defines Cyclin-Dependent Kinase Inhibitor-Sensitive Cells-of-Origin in Esophageal Squamous Cell Carcinoma.Gastro hep advances · 2026Article
- Reframing small cell lung cancer: therapeutic lessons from hematologic malignancies.Frontiers in oncology · 2026Review
- The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026Review
- Deciphering precursor cell dynamics in esophageal preneoplasia via genetic barcoding and single-cell transcriptomics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular mechanisms and clinical insights in transformed small cell lung cancer: a narrative review.Translational lung cancer research · 2025Review
- Deciphering Precursor Cell Dynamics in Esophageal Preneoplasia via Genetic Barcoding and Single-Cell Transcriptomics.bioRxiv : the preprint server for biology · 2025Article
- [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
- Tumor Heterogeneity and Plasticity in Small Cell Lung Cancer.Lung Cancer (Auckland, N.Z.) · 2025Review
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21 authors.
Funding
Abstract
Small cell lung cancer (SCLC) is an aggressive malignancy with limited therapeutic options. Capping protein inhibiting regulator of actin dynamics (CRACD) that promotes actin polymerization, is frequently inactivated in SCLC. However, the role of CRACD loss in SCLC is unknown. Here we show that CRACD depletion drives neuroendocrine (NE) cell plasticity and immune evasion in SCLC. Mechanistically, CRACD inactivation disrupts actin organization, leading to suppression of Yap1-NOTCH signaling and subsequent NE gene upregulation. Simultaneously, CRACD loss drives EZH2-mediated histone methylation via nuclear actin disruption, leading to repression of MHC-I genes and depletion of CD8⁺ T cells. Consequently, CRACD-downregulated tumors exhibit increased cellular heterogeneity and escape from immune surveillance. Conversely, pharmacological inhibition of EZH2 restores MHC-I expression, reactivates antitumor immunity, and suppresses tumor growth. These findings identify CRACD as a tumor suppressor that constrains cell plasticity and immune evasion, highlighting the CRACD-EZH2-MHC-I axis as a potential therapeutic vulnerability in SCLC.
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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 Socratic graph.