ArticleThe Journal of clinical investigation2016
Loss of gastrokine-2 drives premalignant gastric inflammation and tumor progression.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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
38 citing papers in PubMed, 45 citations in OpenAlex.
- The emerging roles of ITM2A: At the molecular crossroads of development and pathogenesis.iScience · 2026Review
- Human gastric extracellular matrix hydrogels maintain organoid growth and reduce gene expression associated with stemness and inflammation.Biomedical materials (Bristol, England) · 2026Article
- Pharmacological inhibition of LIF signaling reverses PD-L1-mediated immune suppression in gastric cancer.Translational oncology · 2026Article
- Spatial transcriptomics defines IM-crypt as a premalignant niche with bidirectional divergence in early gastric carcinogenesis.Communications biology · 2026Article
- Precancerous pathways to gastric cancer: a review of experimental animal models recapitulating the correa cascade.Frontiers in cell and developmental biology · 2025Review
- The expression of genes in different sites of gut tract regulates the meat quality of semitendinosus muscle in sheep and goats.Frontiers in veterinary science · 2025Article
- A critical review onFrontiers in cellular and infection microbiology · 2025Review
- Sex differences in the tumor promoting effects of tobacco smoke in a cRaf transgenic lung cancer disease model.Archives of toxicology · 2024Article
- IL-33 Accelerates Chronic Atrophic Gastritis through AMPK-ULK1 Axis Mediated Autolysosomal Degradation of GKN1.International journal of biological sciences · 2024Article
- Quantitative Proteomic Analysis Reveals Yeast Cell Wall Products Influence the Serum Proteome Composition of Broiler Chickens.International journal of molecular sciences · 2022Article
- Helicobacter pylori shows tropism to gastric differentiated pit cells dependent on urea chemotaxis.Nature communications · 2022Article
- Morbid Obesity in Women Is Associated with an Altered Intestinal Expression of Genes Related to Cancer Risk and Immune, Defensive, and Antimicrobial Response.Biomedicines · 2022Article
- IL-33 promotes gastric tumour growth in concert with activation and recruitment of inflammatory myeloid cells.Oncotarget · 2022Article
- Discoveries in Pancreatic Physiology and Disease Biology Using Single-Cell RNA Sequencing.Frontiers in cell and developmental biology · 2021Review
- Chronic stress accelerates the process of gastric precancerous lesions in rats.Journal of Cancer · 2021Article
- Gastrokine 2 Regulates the Antitumor Effect of JAK2/STAT3 Pathway in Gastric Cancer.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Trefoil factor 1 and gastrokine 2 inhibitOncology letters · 2020Article
- Genome-wide transcriptional analysis ofPharmaceutical biology · 2020Article
- Single-cell transcriptomes of pancreatic preinvasive lesions and cancer reveal acinar metaplastic cells' heterogeneity.Nature communications · 2020Article
- Coordinate expression loss ofAmerican journal of physiology. Gastrointestinal and liver physiology · 2020Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
Chronic mucosal inflammation is associated with a greater risk of gastric cancer (GC) and, therefore, requires tight control by suppressive counter mechanisms. Gastrokine-2 (GKN2) belongs to a family of secreted proteins expressed within normal gastric mucosal cells. GKN2 expression is frequently lost during GC progression, suggesting an inhibitory role; however, a causal link remains unsubstantiated. Here, we developed Gkn2 knockout and transgenic overexpressing mice to investigate the functional impact of GKN2 loss in GC pathogenesis. In mouse models of GC, decreased GKN2 expression correlated with gastric pathology that paralleled human GC progression. At baseline, Gkn2 knockout mice exhibited defective gastric epithelial differentiation but not malignant progression. Conversely, Gkn2 knockout in the IL-11/STAT3-dependent gp130F/F GC model caused tumorigenesis of the proximal stomach. Additionally, gastric immunopathology was accelerated in Helicobacter pylori-infected Gkn2 knockout mice and was associated with augmented T helper cell type 1 (Th1) but not Th17 immunity. Heightened Th1 responses in Gkn2 knockout mice were linked to deregulated mucosal innate immunity and impaired myeloid-derived suppressor cell activation. Finally, transgenic overexpression of human gastrokines (GKNs) attenuated gastric tumor growth in gp130F/F mice. Together, these results reveal an antiinflammatory role for GKN2, provide in vivo evidence that links GKN2 loss to GC pathogenesis, and suggest GKN restoration as a strategy to restrain GC progression.
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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.