ArticleJournal of experimental & clinical cancer research : CR2019
Pre-metastatic niche triggers SDF-1/CXCR4 axis and promotes organ colonisation by hepatocellular circulating tumour cells via downregulation of Prrx1.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- Molecular Mechanisms and Immune Regulation in Prostate Cancer: A Review.International journal of molecular sciences · 2026Review
- The pre-metastatic niche: mechanisms, heterogeneity, and therapeutic opportunities.Molecular cancer · 2026Review
- The Pre-metastatic Niche-related Index Reveals the Immune Signature and Immunotherapy Response in Lung Adenocarcinoma.Current medicinal chemistry · 2026Article
- On the potential origin of the zygote-like cancer stem cell with a focus on fusion for cell rescue.Frontiers in cell and developmental biology · 2026Article
- Prrx1 promotes mesangial cell proliferation and kidney fibrosis through YAP in diabetic nephropathy.Journal of pharmaceutical analysis · 2025Article
- Review
- CXCL12 alone is enough to Reprogram Normal Fibroblasts into Cancer-Associated Fibroblasts.Cell death discovery · 2025Article
- Tumour cell-released autophagosomes promote lung metastasis by upregulating PD-L1 expression in pulmonary vascular endothelial cells in breast cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Review
- New insights into the correlations between circulating tumor cells and target organ metastasis.Signal transduction and targeted therapy · 2023Review
- Is cancer an intelligent species?Cancer metastasis reviews · 2023Review
- Article
- Surgical Treatment of Osteosarcoma Induced Distant Pre-Metastatic Niche in Lung to Facilitate the Colonization of Circulating Tumor Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Tumor cell-released LC3-positive EVs promote lung metastasis of breast cancer through enhancing premetastatic niche formation.Cancer science · 2022Article
- CD44 potentiates hepatocellular carcinoma migration and extrahepatic metastases via the AKT/ERK signaling CXCR4 axis.Annals of translational medicine · 2022Article
- Circulating Tumor Cells in Hepatocellular Carcinoma: A Comprehensive Review and Critical Appraisal.International journal of molecular sciences · 2021Review
- Correction to: Pre-metastatic niche triggers SDF-1/CXCR4 axis and promotes organ colonisation by hepatocellular circulating tumour cells via downregulation of Prrx1.Journal of experimental & clinical cancer research : CR · 2021Article
- Efficacy of Postoperative Adjuvant Transcatheter Arterial Chemoembolization in Hepatocellular Carcinoma Patients with Mesenchymal Circulating Tumor Cell.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2021Article
- Prrx1 promotes stemness and angiogenesis via activating TGF-β/smad pathway and upregulating proangiogenic factors in glioma.Cell death & disease · 2021Article
- PRRX1 deficiency induces mesenchymal-epithelial transition through PITX2/miR-200-dependent SLUG/CTNNB1 regulation in hepatocellular carcinoma.Cancer science · 2021Article
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCirculating tumour cells (CTCs), especially mesenchymal CTCs, are important determinants of metastasis, which leads to most recurrence and mortality in hepatocellular carcinoma (HCC). However, little is known about the underlying mechanisms of CTC colonisation in pre-metastatic niches.
methodsDetection and classification of CTCs in patients were performed using the CanPatrol™ system. A lentiviral vector expressing Prrx1-targeting shRNA was constructed to generate a stable HCC cell line with low expression of Prrx1. The effect of Prrx1 knockdown on stemness, migration, and drug resistance of the cell line was assessed, including involvement of SDF-1/CXCR4 signalling. Promising clinical applications of an inhibitor of STAT3 tyrosine phosphorylation, C188-9, and specific blockade with CXCR4 antibody were explored.
resultsThe number of mesenchymal CTCs in blood was closely associated with tumour recurrence or metastasis. Pre-metastatic niche-derived SDF-1 could downregulate Prrx1, which induced the stemness, drug resistance, and increased expression of CXCR4 in HCC cells through the STAT3 pathway in vitro. In vivo, mice bearing tumours of Prrx1 low-expressing cells had significantly shorter survival. In xenograft tumours and clinical samples, loss of Prrx1 was negatively correlated with increased expression of CXCR4 in lung metastatic sites compared with that in the primary foci.
conclusionsThese findings demonstrate that decreased expression of Prrx1 stimulates SDF-1/CXCR4 signalling and contributes to organ colonisation with blood CTCs in HCC. STAT3 inhibition and specific blockade of CXCR4 have clinical potential as therapeutics for eliminating organ metastasis in advanced HCC.
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