ArticleCellular oncology (Dordrecht, Netherlands)2023
Tumor-associated macrophage-derived GDNF promotes gastric cancer liver metastasis via a GFRA1-modulated autophagy flux.
Article in Cellular oncology (Dordrecht, Netherlands), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 28 citations in OpenAlex.
- Remodeling the tumor immune microenvironment: mechanisms of crosstalk between regulated cell death macrophages.Frontiers in immunology · 2026Review
- A Novel Prognostic Signature Composed of Autophagy and Liver Metastasis in Colorectal Cancer: Comprehensive Analysis of Bulk and Single-Cell Transcriptomic Data.ImmunoTargets and therapy · 2026Article
- Tumor-associated macrophages in gastric cancer peritoneal metastasis: orchestrating immune evasion, niche remodeling, and therapeutic resistance.Frontiers in immunology · 2026Review
- Cancer and neurotransmitter receptors.Chinese medical journal · 2025Review
- The role of calcium signaling in organotropic metastasis of cancer.Acta pharmacologica Sinica · 2025Review
- TNS4 promotes lymph node metastasis of gastric cancer by interacting with integrin Β1 and inducing the activation of fibroblastic reticular cell.Cancer cell international · 2025Article
- High extracellular matrix stiffness upregulates TNNT1 to awaken dormant tumor cells in liver metastatic niches of gastric cancer.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Research progress on monocyte/macrophage in the development of gastric cancer.Future oncology (London, England) · 2025Review
- Mechanism and role of H. pylori CagA-induced NLRP3 inflammasome in gastric cancer immune cell infiltration.Scientific reports · 2025Article
- Review
- Circulating inflammatory cytokines and colorectal cancer: New insights from Mendelian randomization.Medicine · 2025Article
- The role of macrophages in liver metastasis: mechanisms and therapeutic prospects.Frontiers in immunology · 2025Review
- Targeting tumor-associated macrophages in gastric cancer progression and therapy: insights from molecular mechanisms to therapeutic applications.Frontiers in pharmacology · 2025Review
- Expression patterns and diagnostic efficacy of cytokeratin 19 and galectin-3 in thyroid neoplasms.International journal of clinical and experimental pathology · 2025Article
- Molecular Mechanism for Malignant Progression of Gastric Cancer Within the Tumor Microenvironment.International journal of molecular sciences · 2024Review
- Impact of liver metastasis on immunotherapy in gastric carcinoma.World journal of gastrointestinal surgery · 2024Article
- Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives.Signal transduction and targeted therapy · 2024Review
- Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis.World journal of gastrointestinal surgery · 2024Article
- Dissecting gastric cancer heterogeneity and exploring therapeutic strategies using bulk and single-cell transcriptomic analysis and experimental validation of tumor microenvironment and metabolic interplay.Frontiers in pharmacology · 2024Article
- The SLITRK4-CNPY3 axis promotes liver metastasis of gastric cancer by enhancing the endocytosis and recycling of TrkB in tumour cells.Cellular oncology (Dordrecht, Netherlands) · 2023Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeLiver metastasis, a lethal malignancy of gastric cancer (GC) patients, execrably impairs their prognosis. As yet, however, few studies have been designed to identify the driving molecules during its formation, except screening evidence pausing before their functions or mechanisms. Here, we aimed to survey a key driving event within the invasive margin of liver metastases.
methodsA metastatic GC tissue microarray was used for exploring malignant events during liver-metastasis formation, followed by assessing the expression patterns of glial cell-derived neurotrophic factor (GDNF) and GDNF family receptor alpha 1 (GFRA1). Their oncogenic functions were determined by both loss- and gain-of-function studies in vitro and in vivo, and validated by rescue experiments. Multiple cell biological studies were performed to identify the underlying mechanisms.
resultsIn the invasive margin, GFRA1 was identified as a pivotal molecule involved in cellular survival during liver metastasis formation, and we found that its oncogenic role depends on tumor associated macrophage (TAM)-derived GDNF. In addition, we found that the GDNF-GFRA1 axis protects tumor cells from apoptosis under metabolic stress via regulating lysosomal functions and autophagy flux, and participates in the regulation of cytosolic calcium ion signalling in a RET-independent and non-canonical way.
conclusionFrom our data we conclude that TAMs, homing around metastatic nests, induce the autophagy flux of GC cells and promote the development of liver metastasis via GDNF-GFRA1 signalling. This is expected to improve the comprehension of metastatic pathogenesis and to provide a novel direction of research and translational strategies for the treatment of metastatic GC patients.
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