ArticleThe Journal of clinical investigation2012
Tpl2 regulates intestinal myofibroblast HGF release to suppress colitis-associated tumorigenesis.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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.
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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
39 citing papers in PubMed, 67 citations in OpenAlex.
- Advances in molecular mechanisms of inflammatory bowel disease‑associated colorectal cancer (Review).Oncology letters · 2024Review
- Article
- Tamoxifen administration induces histopathologic changes within the lungs of Cre-recombinase-negative mice: A case report.Laboratory animals · 2022Article
- Cell adhesion tunes inflammatory TPL2 kinase signal transduction.Cellular and molecular life sciences : CMLS · 2022Article
- Influenza-induced Tpl2 expression within alveolar epithelial cells is dispensable for host viral control and anti-viral immunity.PloS one · 2022Article
- Essential immune functions of fibroblasts in innate host defense.Frontiers in immunology · 2022Review
- Col6a1Cellular and molecular life sciences : CMLS · 2021Article
- Fibroblast Subsets in Intestinal Homeostasis, Carcinogenesis, Tumor Progression, and Metastasis.Cancers · 2021Review
- Fibroblast Reprogramming in Gastrointestinal Cancer.Frontiers in cell and developmental biology · 2020Review
- Tumor progression locus 2 (TPL2) in tumor-promoting Inflammation, Tumorigenesis and Tumor Immunity.Theranostics · 2020Review
- Cellular Interactions in the Intestinal Stem Cell Niche.Archivum immunologiae et therapiae experimentalis · 2019Review
- Innate Sensing through Mesenchymal TLR4/MyD88 Signals Promotes Spontaneous Intestinal Tumorigenesis.Cell reports · 2019Article
- Inhibition of HGF/MET signaling decreases overall tumor burden and blocks malignant conversion in Tpl2-related skin cancer.Oncogenesis · 2019Article
- Hypoxia potentiates monocyte-derived dendritic cells for release of tumor necrosis factor α via MAP3K8.Bioscience reports · 2018Article
- TPL2 Is a Key Regulator of Intestinal Inflammation in Clostridium difficile Infection.Infection and immunity · 2018Article
- Myeloid cell deficiency of p38γ/p38δ protects against candidiasis and regulates antifungal immunity.EMBO molecular medicine · 2018Article
- Review
- miR-589-5p inhibits MAP3K8 and suppresses CD90Journal of experimental & clinical cancer research : CR · 2016Article
- TPL-2 Regulates Macrophage Lipid Metabolism and M2 Differentiation to Control TH2-Mediated Immunopathology.PLoS pathogens · 2016Article
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tumor microenvironment plays a significant role in colitis-associated cancer (CAC). Intestinal myofibroblasts (IMFs) are cells in the intestinal lamina propria secreting factors that are known to modulate carcinogenesis; however, the physiological role of IMFs and signaling pathways influencing CAC have remained unknown. Tumor progression locus 2 (Tpl2) is a MAPK that regulates inflammatory and oncogenic pathways. In this study we addressed the role of Tpl2 in CAC using complete and tissue-specific ablation of Tpl2 in mutant mice. Tpl2-deficient mice did not exhibit significant differences in inflammatory burdens following azoxymethane (AOM)/dextran sodium sulfate (DSS) administration compared with wild-type mice; however, the mutant mice developed significantly increased numbers and sizes of tumors, associated with enhanced epithelial proliferation and decreased apoptosis. Cell-specific ablation of Tpl2 in IMFs, but not in intestinal epithelial or myeloid cells, conferred a similar susceptibility to adenocarcinoma formation. Tpl2-deficient IMFs upregulated HGF production and became less sensitive to the negative regulation of HGF by TGF-β3. In vivo inhibition of HGF-mediated c-Met activation blocked early, enhanced colon dysplasia in Tpl2-deficient mice, indicating that Tpl2 normally suppresses the HGF/c-Met pathway. These findings establish a mesenchyme-specific role for Tpl2 in the regulation of HGF production and suppression of epithelial tumorigenesis.
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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.