ArticleCancer immunology, immunotherapy : CII2023
DLGAP5 promotes gallbladder cancer migration and tumor-associated macrophage M2 polarization by activating cAMP.
Article in Cancer immunology, immunotherapy : CII, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 16 citations in OpenAlex.
- Prognostic Value of Perioperative Inflammatory-Immune-Nutritional Indicators in Advanced Gallbladder Cancer.Cancer medicine · 2026Article
- M2 Macrophage Polarization Characterizes an Immunosuppressive Microenvironment in Extracranial Arteriovenous Malformations.Biomedicines · 2026Article
- YY1-induced upregulation of DLGAP5 promotes tumor progression in lung adenocarcinoma via Wnt/β-catenin/EMT pathway.Journal of translational medicine · 2026Article
- DLGAP5 promotes salivary adenoid cystic carcinoma proliferation and metastasis through PI3K/AKT pathway.American journal of cancer research · 2026Article
- Integrative Bioinformatics and Experimental Validation Establish CCNB1 as a Potential Biomarker for Diagnosis and Prognosis in Colorectal Cancer.Current issues in molecular biology · 2025Article
- Bioinformatics Analysis Reveals the Role of DLGAP4 in the Development and Progression of Hepatocellular Carcinoma.Journal of gastrointestinal cancer · 2025Article
- Bioinformatics analysis of DLGAP5 as a biomarker in lung adenocarcinoma: implications for immune infiltration and targeted therapy.Discover oncology · 2025Article
- Single-cell analyses unravel ecosystem dynamics and intercellular crosstalk during gallbladder cancer malignant transformation.Hepatology communications · 2025Article
- Identification and validation of shared biomarkers and drug repurposing in psoriasis and Crohn's disease: integrating bioinformatics, machine learning, and experimental approaches.Frontiers in immunology · 2025Article
- DLGAP5 enhances bladder cancer chemoresistance by regulating glycolysis through MYC stabilization.Theranostics · 2025Article
- M2-like tumor-associated macrophage-secreted CCL2 facilitates gallbladder cancer stemness and metastasis.Experimental hematology & oncology · 2024Article
- New trends in diagnosis and management of gallbladder carcinoma.World journal of gastrointestinal oncology · 2024Review
- Integrated bioinformatics analysis and experimental validation reveals hub genes of rheumatoid arthritis.Experimental and therapeutic medicine · 2023Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAlthough disc large associated protein family (DLGAP5) has been reported to be involved in a variety of tumor pathologic processes, its expression and mechanism in gallbladder cancer (GBC) are still uncertain. Macrophages were divided into M1 and M2 macrophages. TAM is more closely defined as M2 polarized macrophages, which plays a key role in cancer progression.
objectiveTo clarify the role of disc large associated protein family (DLGAP5) in gallbladder cancer (GBC) progression and investigate the mechanism.
methodsDifferential genes in 10 normal paracancer tissues and 10 GBC tissues in GSE139682 from NCBI-GEO were analyzed by R language. Bioinformation analysis and clinical sample analysis were performed to detect DLGAP5 expression in GBC and its correlation with prognosis. CCK-8, EDU, transwell, wound closure, and Immunoblot were performed to detect its effects on the function of GBC cells. GST-pulldown showed the direct interact between DLGAP5 and cAMP. Macrophage polarization assay was further conducted to detect the effects of DLGAP5 on macrophage M2 polarization. The tumor growth assays were further conducted to confirm its role in mice.
resultsBiological analysis and clinical samples confirmed that DLGAP5 was increased in GBC and strongly related to poor prognosis in patients with GBC. After overexpression of DLGAP5 in GBC cell lines, such as GBC-SD and NOZ cells, cell proliferation and migration were enhanced, and macrophages were polarized to M2. However, after DLGAP5 is knocked down, there is opposite effect. Mechanistically, DLGAP5 promotes the growth and migration of GBC-SD and NOZ cells and the M2 polarization of THP-1-derived macrophages by activating cyclic adenosine monophosphate (cAMP) pathway. In vivo, GBC-SD with DLGAP5 knockdown was subcutaneously injected into nude mice. It was found that after DLGAP5 knockdown, both tumor volume and tumor were reduced, and indicators related to proliferation and M2 polarization decreased.
conclusionOur study shows that DLGAP5 is significantly elevated in GBC and is strongly related to poor prognosis in patients with GBC. DLGAP5 promotes GBC proliferation, migration, and M2 polarization of macrophages through cAMP pathway, which provides a theoretical basis for the treatment of GBC and may become a promising therapeutic target.
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