ArticleJournal of experimental & clinical cancer research : CR2017
Maintenance of stemness is associated with the interation of LRP6 and heparin-binding protein CCN2 autocrined by hepatocellular carcinoma.
Article in Journal of experimental & clinical cancer research : CR, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Connective Tissue Growth Factor in Digestive System Cancers: A Review and Meta-Analysis.BioMed research international · 2020Pooled it
- The regulation of LRPs by miRNAs in cancer: influencing cancer characteristics and responses to treatment.Cancer cell international · 2025Review
- Contribution of extracellular vesicles to steatosis-related liver disease and their therapeutic potential.World journal of hepatology · 2024Review
- Multifaceted effects of LRP6 in cancer: exploring tumor development, immune modulation and targeted therapies.Medical oncology (Northwood, London, England) · 2024Review
- LRP6 is a potential biomarker of kidney clear cell carcinoma related to prognosis and immune infiltration.Aging · 2024Article
- Mucin Glycans: A Target for Cancer Therapy.Molecules (Basel, Switzerland) · 2023Review
- The Relationship between LRP6 and Wnt/β-Catenin Pathway in Colorectal and Esophageal Cancer.Life (Basel, Switzerland) · 2023Article
- LRP6/filamentous-actin signaling facilitates osteogenic commitment in mechanically induced periodontal ligament stem cells.Cellular & molecular biology letters · 2023Article
- Heparin and Heparin-Based Drug Delivery Systems: Pleiotropic Molecular Effects at Multiple Drug Resistance of Osteosarcoma and Immune Cells.Pharmaceutics · 2022Review
- The CCN axis in cancer development and progression.Journal of cell communication and signaling · 2021Review
- LRP6 as a biomarker of poor prognosis of breast cancer.Gland surgery · 2021Article
- Regulation of the Low-Density Lipoprotein Receptor-Related Protein LRP6 and Its Association With Disease: Wnt/β-Catenin Signaling and Beyond.Frontiers in cell and developmental biology · 2021Review
- CCN Family Proteins in Cancer: Insight Into Their Structures and Coordination Role in Tumor Microenvironment.Frontiers in genetics · 2021Review
- Inositol hexaphosphate sensitizes hepatocellular carcinoma to oxaliplatin relating inhibition of CCN2-LRP6-β-catenin-ABCG1 signaling pathway.Journal of Cancer · 2021Article
- Human amniotic mesenchymal stem cells inhibit hepatocellular carcinoma in tumour-bearing mice.Journal of cellular and molecular medicine · 2020Article
- High expression of FOXO3 is associated with poor prognosis in patients with hepatocellular carcinoma.Oncology letters · 2020Article
- A Role for the WNT Co-Receptor LRP6 in Pathogenesis and Therapy of Epithelial Cancers.Cancers · 2019Review
- CCN2-MAPK-Id-1 loop feedback amplification is involved in maintaining stemness in oxaliplatin-resistant hepatocellular carcinoma.Hepatology international · 2019Article
- The Roles of Low-Density Lipoprotein Receptor-Related Proteins 5, 6, and 8 in Cancer: A Review.Journal of oncology · 2019Review
- miR-221 stimulates breast cancer cells and cancer-associated fibroblasts (CAFs) through selective interference with the A20/c-Rel/CTGF signaling.Journal of experimental & clinical cancer research : CR · 2018Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe overall response rate of hepatocellular carcinoma (HCC) to chemotherapy is poor. In our previous study, oxaliplatin-resistant HCC is found to exhibit an enhanced stemness, and increased levels of CCN2 and LRP6, while the role of CCN2 and LRP6 in the prognosis of HCC patients, and the interaction regulation mechanism between CCN2 and LRP6 are still unclear.
methodsThe expression levels of CCN2 and LRP6 were detected in large cohorts of HCCs, and functional analyses of CCN2 and LRP6 were performed both in vitro and in vivo. The roles of cell surface heparin sulfate proteoglycans (HSPGs) in the mutual regulatory between CCN2 and LRP6 were verified in HCC, and the interventions of low molecular weight heparin sodium (LMWH) were explored.
resultsCCN2 and LRP6 were overexpressed in HCCs, and the CCN2 and LRP6 levels were positively associated with the malignant phenotypes and poor prognosis of HCCs. LRP6 could significantly upregulate the expression of CCN2. Meanwhile, CCN2 was able to enhance malignant phenotype of HCC cells in a dose-dependent manner through binding with LRP6; and knock-down of LRP6 expression, perturbation of HSPGs, co-incubation of CCN2 with LMWH could significantly block the adhesion of CCN2 to LRP6. LMWH enhanced the therapeutic effect of oxaliplatin on HCC with a high CCN2 expression.
conclusionsCCN2 plays a promoting role in HCC progression through activating LRP6 in a HSPGs-dependent manner. Heparin in combination with chemotherapy has a synergic effect and could be a treatment choice for HCCs with a high CCN2 expression.
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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 OpenQuestion graph.