ArticleScience translational medicine2017
ALK is a therapeutic target for lethal sepsis.
Article in Science translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 72 papers, 2 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
72 citing papers in PubMed, 2 syntheses or guidelines pooled it, 123 citations in OpenAlex.
- The Key Drivers of Brain Injury by Systemic Inflammatory Responses after Sepsis: Microglia and Neuroinflammation.Molecular neurobiology · 2023Pooled it
- Current status and challenges of immunotherapy in ALK rearranged NSCLC.Frontiers in oncology · 2022Pooled it
- Three decades of anaplastic lymphoma kinase: from physiological roles to cancer and immune evasion.Cancer metastasis reviews · 2026Review
- Exploring Functionally Enhanced BLP-Trained Macrophage Subpopulations in S. Aureus Infection: Underlying Mechanisms and Therapeutic Significance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Microvesicle-transferred mitochondria trigger cGAS-STING and reprogram metabolism of macrophages in sepsis.Microbiology spectrum · 2025Article
- BCG-Derived Outer Membrane Vesicles Induce TLR2-Dependent Trained Immunity to Protect Against Polymicrobial Sepsis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Pattern recognition receptors: function, regulation and therapeutic potential.Signal transduction and targeted therapy · 2025Review
- cGAS-STING targeting offers novel therapeutic regimen in sepsis-associated organ dysfunction.Cell biology and toxicology · 2025Review
- A neuroimmune pathway drives bacterial infection.Science advances · 2025Article
- cGAS-STING targeting offers therapy choice in lung diseases.Biology direct · 2025Review
- cGAS-STING Targeting Offers Novel Therapeutic Opportunities in Liver Diseases.Drug design, development and therapy · 2025Review
- Extracellular NCOA4 is a mediator of septic death by activating the AGER-NFKB pathway.Autophagy · 2024Article
- NFE2L2 and SLC25A39 drive cuproptosis resistance through GSH metabolism.Scientific reports · 2024Article
- Acacetin targets STING to alleviate the destabilization of the medial meniscus-induced osteoarthritis in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Characteristics and Risk Factors for Pediatric Sepsis.Current medical science · 2024Article
- Targeting ALK averts ribonuclease 1-induced immunosuppression and enhances antitumor immunity in hepatocellular carcinoma.Nature communications · 2024Article
- Article
- Review
- Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
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- Erratum issued
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Sepsis, a life-threatening organ dysfunction caused by infection, is a major public health concern with limited therapeutic options. We provide evidence to support a role for anaplastic lymphoma kinase (ALK), a tumor-associated receptor tyrosine kinase, in the regulation of innate immunity during lethal sepsis. The genetic disruption of ALK expression diminishes the stimulator of interferon genes (STING)-mediated host immune response to cyclic dinucleotides in monocytes and macrophages. Mechanistically, ALK directly interacts with epidermal growth factor receptor (EGFR) to trigger serine-threonine protein kinase AKT phosphorylation and activate interferon regulatory factor 3 (IRF3) and nuclear factor κB (NF-κB) signaling pathways, enabling STING-dependent rigorous inflammatory responses. Moreover, pharmacological or genetic inhibition of the ALK-STING pathway confers protection against lethal endotoxemia and sepsis in mice. The ALK pathway is up-regulated in patients with sepsis. These findings uncover a key role for ALK in modulating the inflammatory signaling pathway and shed light on the development of ALK-targeting therapeutics for lethal systemic inflammatory disorders.
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What OpenQuestion holds
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.