ArticleCell death & disease2024
HOXD3 promotes the migration and angiogenesis of hepatocellular carcinoma via modifying hepatocellular carcinoma cells exosome-delivered CCR6 and regulating chromatin conformation of CCL20.
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 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- CCL20-CCR6 axis in autoimmune disease and cancer progression: clinical and therapeutic implications.Cell communication and signaling : CCS · 2026Review
- WDHD1 promotes hepatocellular carcinoma progression by affecting the cell cycle and immune evasion.Translational oncology · 2026Article
- Developing blood extracellular vesicle protein biomarkers for hepatocellular carcinoma: mechanisms, methods, and translation.Journal of nanobiotechnology · 2026Review
- LncRNA NEAT1 promotes immunosuppression in gastric cancer under endoplasmic reticulum stress by maintaining the MMolecular cancer · 2026Article
- Multi-omics profiling reveals that ScissorCellular oncology (Dordrecht, Netherlands) · 2026Article
- Identification and Preliminary mRNA Validation of Key Genes Associated with Tolerogenic Dendritic Cells in Keloid Based on Transcriptome Data.Clinical, cosmetic and investigational dermatology · 2026Article
- CEP78 regulates the proliferation and angiogenesis of endothelial cells by mediating microtubule stabilization via p150glued.Journal of molecular histology · 2025Article
- The recent progress of tumor cell-derived exosomes in the pathogenesis, diagnosis and therapeutic strategies of tumors.Journal of translational medicine · 2025Review
- CCL20 in the tumor microenvironment: implications for cancer progression and therapeutic approaches.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- The 3D Language of Cancer: Communication via Extracellular Vesicles from Tumor Spheroids and Organoids.International journal of molecular sciences · 2025Review
- Chemokines: Orchestration of the Tumor Microenvironment and Control of Hepatocellular Carcinoma Progression.Cancer medicine · 2025Review
- [Research progress on the involvement of exosome-mediated intercellular communication in the remodeling and the regulation of invasion and metastasis in the hepatocellular tumor microenvironment].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- miR-183-5p-enriched extracellular vesicles promote the crosstalk between hepatocellular carcinoma cell and endothelial cell via SIK1/PI3K/AKT and CCL20/CCR6 signaling pathways.Frontiers in oncology · 2025Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Angiogenesis plays an essential role in the microenvironment of hepatocellular carcinoma (HCC). HOXD3 is involved in the metastasis and invasion of HCC cells; Whereas the underlying molecular mechanisms in the microenvironment of HCC remain unknown. Wound healing, transwell invasion, tube formation and spheroid sprouting assays were carried out to identify the effects of HCC-HOXD3-exosomes and genes on the migration of HCC cells. ChIP-PCR was applied to test the binding region of HOXD3 on CCR6, Med15, and CREBBP promoter. Exosome isolation and mRNA-seq were applied to examine the morphological characteristics of exosomes and the contained mRNA in exosomes. Co-IP and Immunofluorescence assays were used to demonstrate the role of CREBBP in the chromatin conformation of CCL20. The nude mice were used to identify the function of genes in regulating migration of HCC in vivo. In this study, integrated cellular and bioinformatic analyses revealed that HOXD3 targeted the promoter region of CCR6 and induced its transcription. CCR6 was delivered by exosomes to endothelial cells and promoted tumour migration. Overexpression of CCR6 promoted metastasis, invasion in HCCs and angiogenesis in endothelial cells (ECs), whereas its downregulation suppressed these functions. The role of HOXD3 in the metastasis and invasion of HCC cells was reversed after the suppression of CCR6. Furthermore, CCL20 was demonstrated as the ligand of CCR6, and its high expression was found in HCC tissues and cells, which was clinically associated with the poor prognosis of HCC. Mechanistically, HOXD3 targets the promoter regions of CREBBP and Med15, which affect CCL20 chromatin conformation by regulating histone acetylation and expression of Pol II to enhance the migration of HCCs. This study demonstrated the function of the HOXD3-CREBBP/Med15-CCL20-CCR6 axis in regulating invasion and migration in HCC, thus providing new therapeutic targets for HCC.
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