ArticleJournal of experimental & clinical cancer research : CR2014
Blockade of CXCL12/CXCR4 signaling inhibits intrahepatic cholangiocarcinoma progression and metastasis via inactivation of canonical Wnt pathway.
Article in Journal of experimental & clinical cancer research : CR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 74 citations in OpenAlex.
- Decoding the cholangiocarcinoma tumor microenvironment: from single-cell and spatial atlases to translational therapeutic targeting.Journal of translational medicine · 2026Review
- Mechanistic insights into polyphenolic constituents from traditional Chinese medicines in inhibiting colorectal cancer metastasis.Natural products and bioprospecting · 2026Review
- Transcriptomic analysis identifies CXCL12 as a novel candidate gene for litter size in rabbits.Animal bioscience · 2026Article
- Harnessing cellular immunotherapy for cholangiocarcinoma: an integrated roadmap for overcoming resistance.Frontiers in immunology · 2026Review
- CXCR4/CXCL12 axis promotes lymphatic metastasis in tongue squamous cell carcinoma via PI3K/AKT signaling pathway.Journal of translational medicine · 2025Article
- Potential of C-X-C-Chemokine-Receptor-Type-4-Directed PET/CT Using [¹⁸F]AlF-NOTA-QHY-04 in Identifying Molecular Subtypes of Small Cell Lung Cancer.Korean journal of radiology · 2025Article
- CXCR4 promotes tumor stemness maintenance and CDK4/6 inhibitors resistance in ER-positive breast cancer.Breast cancer research : BCR · 2025Article
- The Immune-Genomics of Cholangiocarcinoma: A Biological Footprint to Develop Novel Immunotherapies.Cancers · 2025Review
- CAF-mediated regulation of prostate cancer stem cell stemness via the Wnt/β-catenin and SDF-1/CXCR4 pathways in castration-resistant prostate cancer.Frontiers in cell and developmental biology · 2025Article
- Transcriptome insights into newcastle disease virus-mediated eradication of cholangiocarcinoma cells.PloS one · 2025Article
- Epigenetic Biomarkers and the Wnt/β-Catenin Pathway in Opisthorchis viverrini-associated Cholangiocarcinoma: A Scoping Review on Therapeutic Opportunities.PLoS neglected tropical diseases · 2024Article
- A combination therapy of bortezomib, CXCR4 inhibitor, and checkpoint inhibitor is effective in cholangiocarcinomaiScience · 2023Article
- Current Status ofDiagnostics (Basel, Switzerland) · 2022Review
- The chemokine receptor CXCR4 regulates satellite cell activation, early expansion, and self-renewal, in response to skeletal muscle injury.Frontiers in cell and developmental biology · 2022Article
- Past, Present and Future: The Relationship Between Circular RNA and Immunity.Frontiers in immunology · 2022Review
- Molecular mechanism and potential therapeutic targets of liver metastasis from gastric cancer.Frontiers in oncology · 2022Review
- NOV/CCN3 Promotes Cell Migration and Invasion in Intrahepatic Cholangiocarcinoma via miR-92a-3p.Genes · 2021Article
- Single cell RNA sequencing of AML initiating cells reveals RNA-based evolution during disease progression.Leukemia · 2021Article
- Natural Polyphenols as Targeted Modulators in Colon Cancer: Molecular Mechanisms and Applications.Frontiers in immunology · 2021Review
- Role of Chemokines in the Biology of Cholangiocarcinoma.Cancers · 2020Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntrahepatic cholangiocarcinoma (IHCC) is the second most frequent primary malignant liver tumor following hepatocellular carcinoma. It is a highly fatal disease and has few therapeutics. The CXC chemokine ligand-12 (CXCL12)/CXC chemokine receptor type 4 (CXCR4) axis has been shown to be involved in tumorgenesis, proliferation, and angiogenesis in a variety of cancers including IHCC. However, its prognostic significance in IHCC is unclear. The purpose of this study was to examine the functional role of CXCR4 in the progression and metastasis of IHCC and explore the underlying mechanism.
methodsThe CXCR4 expression, overall survival, and the clinical characteristics including age, sex, differentiation degree, tumor size, vascular invasion, lymph node metastasis, TNM stage, and T stage were analyzed for 122 IHCC patients. Short hairpin RNA (shRNA) against CXCR4 was used to disrupt the CXCL12/CXCR4 signal transduction pathways in IHCC cell lines. In vitro assays, including CCK-8 assay, flow cytometry, and colony formation assay, and in vivo tumor formation assay were utilized to detect the cell phenotype of CXCR4 knockdown cells. Transwell and wound healing assays were used to examine the IHCC cell invasion and migration ability. The Wnt pathway was assessed by Western blot and β-Catenin/Tcf transcription reporter assay.
resultsWe demonstrated that CXCR4 expression was closely correlated with IHCC progression and metastasis characteristics. The overall survival of patients with high CXCR4 expression was significantly lower than that of patients with low CXCR4 expression. Furthermore, we showed that the abrogation of CXCR4 had significantly negative influence on the IHCC cell phenotype, including in vitro cell proliferation, cell cycle, colony formation, cell invasion, and in vivo tumorigenicity. In addition, CXCR4 knockdown downregulated Wnt target genes and mesenchymal markers such as Vimentin and Slug.
conclusionsIn conclusion, our result shows that high CXCR4 expression is associated with IHCC progression and metastasis via the canonical Wnt pathway, suggesting that CXCR4 may serve as a promising therapeutic target for IHCC.
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