ArticleThe Journal of clinical investigation2023
CAP2 promotes gastric cancer metastasis by mediating the interaction between tumor cells and tumor-associated macrophages.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 76 citations in OpenAlex.
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- Unveiling novel macrophage-specific biomarkers in MASH through single-cell sequencing for diagnostic modeling.Journal of lipid research · 2026Article
- Gastric Cancer: Pathobiology and Therapeutics.MedComm · 2026Review
- Role of histone modifications in gastric cancer (Review).International journal of oncology · 2026Review
- TTC26 scaffolds MINDY3-mediated RACK1 deubiquitination to drive osteoclastogenesis and pathological bone resorption.Journal of orthopaedic translation · 2026Article
- ST3GAL1 drives colorectal cancer metastasis by mediating NRF2-induced activation of the integrin-α6β4 signaling pathway via sialylation modification.Journal of translational medicine · 2026Article
- A novel ferroptosis- and endoplasmic reticulum stress-related gene signature for predicting prognosis, immune features and drug sensitivity in gastric cancer.Discover oncology · 2026Article
- Traditional Chinese medicine modulates tumor-associated macrophages to suppress gastric cancer progression: mechanisms and therapeutic potential.Frontiers in oncology · 2026Review
- Single-Cell Transcriptomic Analysis Suggests That JUN May Regulate BAMBI to Promote Osteosarcoma Cell Migration and Invasion.Human mutation · 2026Article
- The tumor microenvironment shapes gastric cancer progression by coordinating immune suppression and metabolic reprogramming.Frontiers in immunology · 2026Review
- Mechanoresponsive reprogramming of tumor-associated macrophages during cancer progression.Frontiers in cell and developmental biology · 2026Review
- High-Throughput Heterospheroid-Based Screening Identifies Drugs That Reprogram Tumor-Associated Macrophages.Journal of immunology research · 2026Article
- PGE1 Suppresses the Expression of M2 Markers on Macrophages Through Prostaglandin Receptors.Cells · 2025Article
- Single-Cell Transcriptomics Reveals ITGA2-Mediated Metabolic Reprogramming and Immune Crosstalk in Pediatric Thyroid Carcinogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- ZFPL1 Promotes Colorectal Cancer Progression by Stabilizing ASS1 to Drive the Urea Cycle and M2 Macrophage-Mediated Metastatic Colonization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Hypomethylation-mediated upregulation of PHOX1 promotes gastric cancer progression via transactivation of NGFR.Cell death discovery · 2025Article
- Molecular mechanisms of RACK1-driven metastasis in pancreatic ductal adenocarcinoma revealed by single-cell RNA sequencing.Discover oncology · 2025Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The metastasis of cancer cells is the main cause of death in patients with gastric cancer (GC). Mounting evidence has demonstrated the vital importance of tumor-associated macrophages in promoting tumor invasion and metastasis; however, the interaction between tumor cells and macrophages in GC is largely unknown. In this study, we demonstrated that cyclase-associated protein 2 (CAP2) was upregulated in GC, especially in cases with lymph node metastasis, and was correlated with a poorer prognosis. The transcription factor JUN directly bound to the promoter region of CAP2 and activated CAP2 transcription. The N-terminal domain of CAP2 bound to the WD5 to WD7 domains of receptor for activated C kinase 1 (RACK1) and induced M2 macrophage polarization by activating the SRC/focal adhesion kinase (FAK)/ERK signaling pathway, which resulted in IL-4 and IL-10 secretion. Polarized M2 macrophages induced premetastatic niche formation and promoted GC metastasis by secreting TGFB1, which created a TGFB1/JUN/CAP2 positive-feedback loop to activate CAP2 expression continuously. Furthermore, we identified salvianolic acid B as an inhibitor of CAP2, which effectively inhibited GC cell invasion capabilities by suppressing the SRC/FAK/ERK signaling pathway. Our data suggest that CAP2, a key molecule mediating the interaction between GC cells and tumor-associated macrophages, may be a promising therapeutic target for suppressing tumor metastasis 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 Socratic graph.