ArticleNature medicine2010
Neutrophil elastase-mediated degradation of IRS-1 accelerates lung tumor growth.
Article in Nature medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 469 papers, 4 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
469 citing papers in PubMed, 4 syntheses or guidelines pooled it, 728 citations in OpenAlex.
- Global trends in tumor-associated neutrophil research: a bibliometric and visual analysis.Frontiers in immunology · 2025Pooled it
- Prognostic and clinicopathological significance of systemic immune-inflammation index in upper tract urothelial carcinoma: a meta-analysis of 3911 patients.Frontiers in oncology · 2024Pooled it
- Prognostic significance of systemic immune-inflammation index in patients with ovarian cancer: a meta-analysis.Frontiers in oncology · 2023Pooled it
- Cutting edges and therapeutic opportunities on tumor-associated macrophages in lung cancer.Frontiers in immunology · 2022Pooled it
- Trial
- Neutrophils in cancer.Nature reviews. Cancer · 2026Review
- MLKL regulates intracellular trafficking of neutrophil elastase to promote lung epithelial cell senescence.American journal of respiratory cell and molecular biology · 2026Article
- A novel "early warning" system for biochemical recurrence in prostate cancer: development and validation of the SII-HALP combined score.BMC cancer · 2026Article
- Cell death crosstalk in NET-Driven inflammation: mechanisms, disease contexts, and therapeutic perspectives.Biomarker research · 2026Review
- New Insights Into the Role of Neutrophils in Lymphoma.Cancer medicine · 2026Review
- Nucleotide signaling in neutrophils: a key player in cancer dynamics.Purinergic signalling · 2026Review
- Platelet-neutrophil cooperation in cancer: mechanisms of metastatic niche formation and implications for prognostic stratification and therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Neutrophil Elastase as a Prognostic Biomarker and Driver of Tumor Progression in Diffuse Large B-Cell Lymphoma.Cancer medicine · 2026Article
- Hijacking emergency granulopoiesis: Neutrophil ontogeny and reprogramming in cancer.Molecular oncology · 2026Review
- Neutrophil Extracellular Traps in Cancer Metastasis: From Mechanistic Understanding to Targeted Therapy.Current oncology (Toronto, Ont.) · 2026Review
- ELANE inhibits the progression of osteosarcoma via suppressing the CXCL12/CXCR4 axis.Molecular and cellular biochemistry · 2026Article
- Neutrophil extracellular traps in cancer.Nature reviews. Cancer · 2026Review
- Improving Prognostic Prediction in Head and Neck Cancer Through a Combined Systemic Immune-Inflammation Index and Prognostic Nutritional Index Score.Current oncology (Toronto, Ont.) · 2026Article
- Neutrophil extracellular traps in tumor microenvironment for radiotherapy: friend or foe?Frontiers in immunology · 2026Review
- Neutrophil Extracellular Traps in Heart Failure: From Pathophysiological Mechanisms to Therapeutic Targets.Journal of inflammation research · 2026Review
409 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
Lung cancer is the leading cause of cancer death worldwide. Recent data suggest that tumor-associated inflammatory cells may modify lung tumor growth and invasiveness. To determine the role of neutrophil elastase (encoded by Elane) on tumor progression, we used the loxP-Stop-loxP K-ras(G12D) (LSL-K-ras) model of mouse lung adenocarcinoma to generate LSL-K-ras-Elane(-/-) mice. Tumor burden was markedly reduced in LSL-K-ras-Elane(-/-) mice at all time points after induction of mutant K-ras expression. Kaplan-Meier survival analysis showed that whereas all LSL-K-ras-Elane(+/+) mice died, none of the mice lacking neutrophil elastase died. Neutrophil elastase directly induced tumor cell proliferation in both human and mouse lung adenocarcinomas by gaining access to an endosomal compartment within tumor cells, where it degraded insulin receptor substrate-1 (IRS-1). Immunoprecipitation studies showed that, as neutrophil elastase degraded IRS-1, there was increased interaction between phosphatidylinositol 3-kinase (PI3K) and the potent mitogen platelet-derived growth factor receptor (PDGFR), thereby skewing the PI3K axis toward tumor cell proliferation. The inverse relationship identified between neutrophil elastase and IRS-1 in LSL-K-ras mice was also identified in human lung adenocarcinomas, thus translating these findings to human disease. This study identifies IRS-1 as a key regulator of PI3K within malignant cells. Additionally, to our knowledge, this is the first description of a secreted proteinase gaining access to the inside of a cell and altering intracellular signaling.
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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 OpenQuestion graph.