ArticleOncotarget2016
De novo HAPLN1 expression hallmarks Wnt-induced stem cell and fibrogenic networks leading to aggressive human hepatocellular carcinomas.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- The extracellular matrix in cancer-associated fibrosis: molecular mechanisms and clinical relevance.JCI insight · 2026Review
- HAPLN1 Exhibits Dual Effects: Facilitating Extracellular Matrix Restoration while Enhancing Inflammatory Mediator Production in Arthritic Chondrocytes.Inflammation · 2025Article
- HAPLN1 potentiates peritoneal metastasis in pancreatic cancer.Nature communications · 2023Article
- Ectopic CH60 mediates HAPLN1-induced cell survival signaling in multiple myeloma.Life science alliance · 2023Article
- Metabolic Networks: Weighted Gene Correlation Network Analysis.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Differences in the stemness characteristics and molecular markers of distinct human oral tissue neural crest-derived multilineage cells.Cell proliferation · 2022Article
- A Hyaluronan and Proteoglycan Link Protein 1 Matrikine: Role of Matrix Metalloproteinase 2 in Multiple Myeloma NF-κB Activation and Drug Resistance.Molecular cancer research : MCR · 2022Article
- Well-differentiated liver cancers reveal the potential link between ACE2 dysfunction and metabolic breakdown.Scientific reports · 2022Article
- HAPLN1 Affects Cell Viability and Promotes the Pro-Inflammatory Phenotype of Fibroblast-Like Synoviocytes.Frontiers in immunology · 2022Article
- Editorial: Novel immunotherapies to treat gastrointestinal solid tumor cancers.Frontiers in oncology · 2022Article
- Comparative Proteomic Analysis to Investigate the Pathogenesis of Oral Adenoid Cystic Carcinoma.ACS omega · 2021Article
- Article
- Identification of Methylation-Regulated Differentially Expressed Genes and Related Pathways in Hepatocellular Carcinoma: A Study Based on TCGA Database and Bioinformatics Analysis.Frontiers in oncology · 2021Article
- Novel role of ASH1L histone methyltransferase in anaplastic thyroid carcinoma.The Journal of biological chemistry · 2020Article
- Metformin, an AMPK Activator, Inhibits Activation of FLSs but Promotes HAPLN1 Secretion.Molecular therapy. Methods & clinical development · 2020Article
- Porcine Vocal Fold Lamina Propria-Derived Biomaterials Modulate TGF-β1-Mediated Fibroblast Activation in Vitro.ACS biomaterials science & engineering · 2020Article
- Identification of key candidate genes and pathways in follicular variant papillary thyroid carcinoma by integrated bioinformatical analysis.Translational cancer research · 2020Article
- Anti-cancer effect of dung beetle glycosaminoglycans on melanoma.BMC cancer · 2019Article
- Dimensions of hepatocellular carcinoma phenotypic diversity.World journal of gastroenterology · 2018Review
- Identification of potential pathogenic biomarkers in clear cell renal cell carcinoma.Oncology letters · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
About 20% hepatocellular carcinomas (HCCs) display wild-type β-catenin, enhanced Wnt signaling, hepatocyte dedifferentiation and bad outcome, suggesting a specific impact of Wnt signals on HCC stem/progenitor cells. To study Wnt-specific molecular pathways, cell fates and clinical outcome, we fine-tuned Wnt/β-catenin signaling in liver progenitor cells, using the prototypical Wnt ligand Wnt3a. Cell biology assays and transcriptomic profiling were performed in HepaRG hepatic progenitors exposed to Wnt3a after β-catenin knockdown or Wnt inhibition with FZD8_CRD. Gene expression network, molecular pathology and survival analyses were performed on HCCs and matching non-tumor livers from 70 patients by real-time PCR and tissue micro-array-based immunohistochemistry. Wnt3a reprogrammed liver progenitors to replicating fibrogenic myofibroblast-like cells displaying stem and invasive features. Invasion was inhibited by 30 nM FZD7 and FZD8 CRDs. Translation of these data to human HCCs revealed two tight gene networks associating cell surface Wnt signaling, stem/progenitor markers and mesenchymal commitment. Both networks were linked by Hyaluronan And Proteoglycan Link Protein 1 (HAPLN1), that appeared de novo in aggressive HCCs expressing cytoplasmic β-catenin and stem cell markers. HAPLN1 was independently associated with bad overall and disease-free outcome. In vitro, HAPLN1 was expressed de novo in EPCAM¯/NCAM+ mesoderm-committed progenitors, upon spontaneous epithelial-mesenchymal transition and de-differentiation of hepatocyte-like cells to liver progenitors. In these cells, HAPLN1 knockdown downregulated key markers of mesenchymal cells, such as Snail, LGR5, collagen IV and α-SMA. In conclusion, HAPLN1 reflects a signaling network leading to stemness, mesenchymal commitment and HCC progression.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.