ArticleCell death & disease2024
Tumor-secreted LCN2 impairs gastric cancer progression via autocrine inhibition of the 24p3R/JNK/c-Jun/SPARC axis.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Bibliometric analysis of tumor marker application in gastric cancer diagnosis from 2019 to 2024.Frontiers in medicine · 2025Pooled it
- Astrocytic LCN2 mediates pathological crosstalk with neurons to promote neuronal loss in sepsis-associated encephalopathy.Cell death and differentiation · 2026Article
- Immune, molecular and genetic profiles of gastric signet ring cell carcinoma: Recent progress and future challenges.International journal of cancer · 2026Review
- Targeting NRP1 in Endothelial Cells Facilitates the Normalization of Scar Vessels and Prevents Fibrotic Scarring.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Bidirectional Mendelian Randomisation Analysis of Gastric Cancer and Depression: Evidence for the Causal Effect of Cancer on Depression.Actas espanolas de psiquiatria · 2026Article
- Exosome-derived Menin from cancer-associated fibroblasts promotes gastric cancer progression by activating the HSPA6/JNK/JunD pathway and inducing EMT.Journal of translational medicine · 2025Article
- An LCN2-Dependent Positive-Feedback Loop Between Gastric Cancer Cells and Tumor-Associated-Macrophages Mediates Lymphangiogenesis and Lymphatic Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Regulatory Mechanisms of SPARC Overexpression in Melanoma Progression.International journal of molecular sciences · 2025Article
- Extracellular matrix dynamics in tumor immunoregulation: from tumor microenvironment to immunotherapy.Journal of hematology & oncology · 2025Review
- The heterogeneous roles of neutrophils in gastric cancer: scaffold or target?Cellular & molecular biology letters · 2025Review
- Identification of stemness subtypes and prognostic modeling in thyroid cancer: the critical role of DPYSL3 in tumor progression and immune microenvironment.Discover oncology · 2025Article
- Lipocalin-2-mediated ferroptosis as a target for protection against light-induced photoreceptor degeneration.Molecular medicine (Cambridge, Mass.) · 2025Article
- Identification of Anoikis-Related Genes in Gastric Cancer: Bioinformatics and Experimental Validation.Cancer medicine · 2025Article
- Analyze the Diversity and Function of Immune Cells in the Tumor Microenvironment From the Perspective of Single-Cell RNA Sequencing.Cancer medicine · 2025Review
- An integrative analysis reveals cancer risk associated with artificial sweeteners.Journal of translational medicine · 2025Article
- Development and verification of lymphangiogenesis score for prediction of prognosis and immune landscape in gastric cancer.Frontiers in immunology · 2025Article
- The role of the C5a-C5aR pathway in iron metabolism and gastric cancer progression.Frontiers in immunology · 2024Article
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gastric cancer (GC) is one of the most lethal malignancies worldwide. Despite extensive efforts to develop novel therapeutic targets, effective drugs for GC remain limited. Recent studies have indicated that Lipocalin (LCN)2 abnormalities significantly impact GC progression; however, its regulatory network remains unclear. Our study investigates the functional role and regulatory mechanism of action of LCN2 in GC progression. We observed a positive correlation between LCN2 expression, lower GC grade, and better prognosis in patients with GC. LCN2 overexpression suppressed GC proliferation and metastasis both in vitro and in vivo. Transcriptome sequencing identified secreted protein acidic and rich in cysteine (SPARC) as a pivotal downstream target of LCN2. Mechanistically, c-Jun acted as a transcription factor inducing SPARC expression, and LCN2 downregulated SPARC by inhibiting the JNK/c-Jun pathway. Moreover, LCN2 bound to its receptor, 24p3R, via autocrine signaling, which directly inhibited JNK phosphorylation and then inhibited the JNK/c-Jun pathway. Finally, analysis of clinical data demonstrated that SPARC expression correlated negatively with lower GC grade and better prognosis, and that LCN2 expression correlated negatively with p-JNK, c-Jun, and SPARC expression in GC. These findings suggest that the LCN2/24p3R/JNK/c-Jun/SPARC axis is crucial in the malignant progression of GC, offering novel prognostic markers and therapeutic targets.
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