ArticleJCI insight2024
Blocking the angiopoietin-2-dependent integrin β-1 signaling axis abrogates small cell lung cancer invasion and metastasis.
Article in JCI insight, 2024. 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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Who cites it
12 citing papers in PubMed.
- Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer.Annals of medicine · 2026Review
- In vitro multi-organ invasion model for exploring cardiac resistance to cancer metastasis.Nature communications · 2026Article
- KTX207-mediated PDE4D degradation disrupts tumour cell migration, invasion, and angiogenic potential.Cell communication and signaling : CCS · 2026Article
- Biomarkers for predominantly inattentive ADHD: potential involvement of Wnt/β-catenin/integrin signaling in a spontaneously hypertensive rat.Genes & genomics · 2026Article
- Efficacy and safety of anlotinib combined with etoposide and platinum-based regimens in the first-line treatment of extensive-stage small-cell lung cancer: a systematic review and meta-analysis.Journal of thoracic disease · 2026Article
- ERBB2 signaling drives immune cell evasion and resistance against immunotherapy in small cell lung cancer.Nature communications · 2025Article
- Integrated pan-cancer and melanoma-specific analysis of angiopoietin-2: prognostic value, immune microenvironment modulation, and ceRNA network regulation.Discover oncology · 2025Article
- A single-cell atlas of bladder cancer unveils dynamic cellular composition and endothelial functional shifts during progression.Discover oncology · 2025Article
- Current and future therapies for small cell lung carcinoma.Journal of hematology & oncology · 2025Review
- Downregulated TRAF3IP2-AS1 promotes hepatocellular carcinoma progression through the miR-374a-5p/SEL1L1/RPL6 axis to enhance DNA damage repair.American journal of translational research · 2025Article
- The multifaceted roles of mucins family in lung cancer: from prognostic biomarkers to promising targets.Frontiers in immunology · 2025Review
- Prognostic significance and immune microenvironment infiltration patterns of hypoxia and endoplasmic reticulum stress-related genes in gastric cancer.Frontiers in oncology · 2025Article
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Authors and funding
22 authors.
Funding
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Abstract
Small cell lung cancer (SCLC) is the most aggressive lung cancer entity with an extremely limited therapeutic outcome. Most patients are diagnosed at an extensive stage. However, the molecular mechanisms driving SCLC invasion and metastasis remain largely elusive. We used an autochthonous SCLC mouse model and matched samples from patients with primary and metastatic SCLC to investigate the molecular characteristics of tumor metastasis. We demonstrate that tumor cell invasion and liver metastasis in SCLC are triggered by an Angiopoietin-2 (ANG-2)/Integrin β-1-dependent pathway in tumor cells, mediated by focal adhesion kinase/Src kinase signaling. Strikingly, CRISPR-Cas9 KO of Integrin β-1 or blocking Integrin β-1 signaling by an anti-ANG-2 treatment abrogates liver metastasis formation in vivo. Interestingly, analysis of a unique collection of matched samples from patients with primary and metastatic SCLC confirmed a strong increase of Integrin β-1 in liver metastasis in comparison with the primary tumor. We further show that ANG-2 blockade combined with PD-1-targeted by anti-PD-1 treatment displays synergistic treatment effects in SCLC. Together, our data demonstrate a fundamental role of ANG-2/Integrin β-1 signaling in SCLC cells for tumor cell invasion and liver metastasis and provide a potentially new effective treatment strategy for patients with SCLC.
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