ArticleScience advances2025
Src/FN1 pathway activation drives tumor cell cluster formation and metastasis in lung cancer: A promising therapeutic target.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Targeting Src/FN1 adhesion circuitry to suppress circulating tumor cell clusters and lung cancer metastasis.Genes & diseases · 2027Article
- NNMT-associated metabolic-thromboinflammatory-immune co-activation in heterogeneous CTC clusters: a hypothesis-generating computational framework".BMC cancer · 2026Article
- [Tumor Cell and Brain Microenvironment Interactions in Non-small Cell Lung Cancer Brain Metastasis: Mechanisms and Emerging Insights].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Single-Cell and Multiomics Characterization of p21 in Cancer Progression and Therapeutic Sensitivity.Human mutation · 2026Article
- A scissor-guided single-cell framework defines a macrophage-derived risk score for prognostic and immunotherapy stratification in lung adenocarcinoma.Frontiers in immunology · 2026Article
- Engineering spherical nucleic acids for precision cancer therapy: design strategies and medical applications.Theranostics · 2026Review
- Histological fidelity and microenvironmental kinome signatures of metastatic patient-derived organoids.Frontiers in bioengineering and biotechnology · 2026Article
- P-glycoprotein 1 as a shared target for resensitizing drug-resistant tumor cells and preventing fibronectin-driven metastasis.Theranostics · 2026Article
- Integrative Single-Cell and Machine Learning Analysis Reveals Immune Microenvironment Remodelling in Lymph Node Metastasis of Lung Adenocarcinoma.Journal of cellular and molecular medicine · 2025Article
- c-MET Inhibition Reverses the Osimertinib Resistance in Lung Circulating Tumor Cell Clusters and Suppresses Metastasis.Biological procedures online · 2025Article
- Protein phosphorylation regulation of key genes in oral squamous cell carcinoma and their role in the immune microenvironment.Frontiers in immunology · 2025Article
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Authors and funding
13 authors.
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Abstract
Lung cancer remains the leading cause of cancer-related death globally, with metastasis driven by circulating tumor cells (CTCs)-particularly clusters-being a major treatment challenge. Despite their critical role, the biological differences between single CTCs and CTC clusters remain unclear. Here, we comprehensively compared their behavioral, transcriptomic, and proteomic profiles in lung cancer models. Compared with single cells, CTC clusters present enhanced metastatic potential, greater survival in the bloodstream and increased resistance to microenvironment. Mechanistically, the Src/FN1 pathway is centrally activated in clusters, promoting intercellular cohesion and protecting against immune clearance and stress in circulation. Pharmacological inhibition of Src with the clinical inhibitor KX2-391 disrupted clustering, impaired CTC survival, and reduced metastasis in preclinical models. Our findings identify the Src/FN1 pathway as a key vulnerability in CTC cluster-driven metastasis, suggesting that Src inhibitors are promising therapeutic strategies to disrupt clustering and improve outcomes in patients with metastatic lung cancer.
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