ArticleThe Journal of clinical investigation2018
Stromal Lkb1 deficiency leads to gastrointestinal tumorigenesis involving the IL-11-JAK/STAT3 pathway.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 72 citations in OpenAlex.
- Peutz-Jeghers syndrome withoutWorld journal of gastroenterology · 2023Trial
- Differential phenotypes in mice with smooth muscle-specific heterozygous versus homozygous deletion of Stk11.Scientific reports · 2025Article
- Cancer-Associated Fibroblasts: Clinical Applications in Imaging and Therapy.Tomography (Ann Arbor, Mich.) · 2025Review
- JAK1/2 Inhibition Delays Cachexia and Improves Survival through Increased Food Intake.bioRxiv : the preprint server for biology · 2025Article
- Interleukin-11 promotes lung adenocarcinoma tumourigenesis and immune evasion.Clinical and translational medicine · 2025Article
- IL-17 links the tumor suppressor LKB1 to gastrointestinal inflammation and polyposis.Science advances · 2025Article
- Immune profiling of premalignant lesions in patients with Peutz-Jeghers syndrome.United European gastroenterology journal · 2025Article
- Gastric-type endocervical adenocarcinoma, superficial myofibroblastoma, sex cord-stromal tumors, and HSIL in Peutz-Jeghers syndrome: a rare case report, genetic characterization, and review of literature.Frontiers in oncology · 2025Article
- Kupffer Cell-derived IL6 Promotes Hepatocellular Carcinoma Metastasis Via the JAK1-ACAP4 Pathway.International journal of biological sciences · 2025Article
- Progress report: Peutz-Jeghers syndrome.Familial cancer · 2024Review
- Understanding interleukin 11 as a disease gene and therapeutic target.The Biochemical journal · 2023Review
- Cancer Risk of Peutz-Jeghers Syndrome and Treatment Experience: A Chinese Medical Center.Clinics in colon and rectal surgery · 2023Review
- STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway.Molecular cancer · 2023Article
- LKB1 controls inflammatory potential through CRTC2-dependent histone acetylation.Molecular cell · 2023Article
- Tellu - an object-detector algorithm for automatic classification of intestinal organoids.Disease models & mechanisms · 2023Article
- Prognostic Value of Liver Kinase B1 (LKB1) in Gastric Cancer-Associated Tumor Microenvironment Immunity.Biomedicines · 2023Article
- IL11 signaling mediates piR-2158 suppression of cell stemness and angiogenesis in breast cancer.Theranostics · 2023Article
- Article
- PTEN and LKB1 are differentially required in Gli1-expressing mesenchymal cells to suppress gastrointestinal polyposis.Cell reports · 2022Article
- mExperimental hematology & oncology · 2022Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Germline mutations in the gene encoding tumor suppressor kinase LKB1 lead to gastrointestinal tumorigenesis in Peutz-Jeghers syndrome (PJS) patients and mouse models; however, the cell types and signaling pathways underlying tumor formation are unknown. Here, we demonstrated that mesenchymal progenitor- or stromal fibroblast-specific deletion of Lkb1 results in fully penetrant polyposis in mice. Lineage tracing and immunohistochemical analyses revealed clonal expansion of Lkb1-deficient myofibroblast-like cell foci in the tumor stroma. Loss of Lkb1 in stromal cells was associated with induction of an inflammatory program including IL-11 production and activation of the JAK/STAT3 pathway in tumor epithelia concomitant with proliferation. Importantly, treatment of LKB1-defcient mice with the JAK1/2 inhibitor ruxolitinib dramatically decreased polyposis. These data indicate that IL-11-mediated induction of JAK/STAT3 is critical in gastrointestinal tumorigenesis following Lkb1 mutations and suggest that targeting this pathway has therapeutic potential in Peutz-Jeghers syndrome.
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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.