ArticleJournal of experimental & clinical cancer research : CR2018
Chitinase 3-like 1-CD44 interaction promotes metastasis and epithelial-to-mesenchymal transition through β-catenin/Erk/Akt signaling in gastric cancer.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 122 citations in OpenAlex.
- Redefining CHI3L1: Therapeutic Opportunities at the Crossroads of Immune Suppression and Disease Progression.Medicinal research reviews · 2026Review
- Context-dependent promotion of epithelial-mesenchymal transition by IL-13Rα2/STAT6 signaling in colorectal cancer.Molecular and cellular biochemistry · 2026Article
- Clonal Hematopoiesis in Colorectal Cancer: Mechanisms and Implications.Cancer medicine · 2026Review
- Bispecific targeting of CHI3L1 and PD-1 as a therapeutic strategy for pulmonary fibrosis.JCI insight · 2026Article
- Host Proteome Remodeling During Group A Streptococcus Skin Infection.Molecular & cellular proteomics : MCP · 2026Article
- CHI3L1 is a diagnostic biomarker involved in immune infiltration of gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- The CHI3L1-neutrophil axis drives immune suppression and breast cancer metastatic dissemination.JCI insight · 2026Article
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- Differential contribution of TFE3 isoforms to cell motility and invasion.EMBO reports · 2026Article
- Kasugamycin Inhibits Melanoma Lung Metastasis and CHI3L1-Driven M2-Like Tumor-Associated Macrophage Differentiation.ImmunoTargets and therapy · 2026Article
- Review
- Nociceptive Nerve-Derived CGRP Exacerbates Uterine Fibrogenesis in Adenomyosis by Promoting CD140bAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- CHI3L1-targeted small molecules as glioblastoma therapies: Virtual screening-based discovery, biophysical validation, pharmacokinetic profiling, and evaluation in glioblastoma spheroids.European journal of medicinal chemistry · 2025Article
- Early metastasis is characterized by Gr1+ cell dysregulation and is inhibited by immunomodulatory nanoparticles.Molecular oncology · 2025Article
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- Future Perspectives and Conclusions from Animal Models of CHI3L1-Related Inflammation-Associated Cancer.Cells · 2025Review
- Multiomic Evidence for a Unified Model of Alzheimer's Disease Etiology Linking Microglial Flux Capacity and Astrocyte-Neuron Metabolic Breakdown.bioRxiv : the preprint server for biology · 2025Article
- CHI3L1: a key driver in gastritis-to-cancer transformation.Journal of translational medicine · 2025Article
- Heparin-binding of the human chitinase-like protein YKL-40 is allosterically modified by chitin oligosaccharides.Biochemistry and biophysics reports · 2025Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundEnzymatically inactive chitinase-like protein CHI3L1 drives inflammatory response and promotes tumor progression. However, its role in gastric cancer (GC) tumorigenesis and metastasis has not yet been fully elucidated. We determined the significance of CHI3L1 expression in patients with GC. We also explored an as-yet unknown receptor of CHI3L1 and investigated the involved signaling in GC metastasis.
methodsCHI3L1 expression was evaluated by immunoblotting, tissue microarray-based immunohistochemistry analysis (n = 100), and enzyme linked immunosorbent assay (ELISA) (n = 150). The interactions between CD44 and CHI3L1 or Interleukin-13 receptor alpha 2 (IL-13Rα2) were analyzed by co-immunoprecipitation, immunofluorescence co-localization assay, ELISA, and bio-layer interferometry. The roles of CHI3L1/CD44 axis in GC metastasis were investigated in GC cell lines and experimental animal model by gain and loss of function.
resultsCHI3L1 upregulation occurred during GC development, and positively correlated with GC invasion depth, lymph node status, and tumor staging. Mechanically, CHI3L1 binding to CD44 activated Erk and Akt, along with β-catenin signaling by phosphorylating β-catenin at Ser552 and Ser675. CD44 also interacted with IL-13Rα2 to form a complex. Notably, CD44v3 peptide and protein, but not CD44v6 peptide or CD44s protein, bound to both CHI3L1 and IL-13Rα2. Our in vivo and in vitro data further demonstrated that CHI3L1 promoted GC cell proliferation, migration, and metastasis.
conclusionsCHI3L1 binding to CD44v3 activates Erk, Akt, and β-catenin signaling, therefore enhances GC metastasis. CHI3L1 expression is a novel biomarker for the prognosis of GC, and these findings have thus identified CHI3L1/CD44 axis as a vital pathway and potential therapeutic target in GC.
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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.