ArticleJournal of experimental & clinical cancer research : CR2020
NCSTN promotes hepatocellular carcinoma cell growth and metastasis via β-catenin activation in a Notch1/AKT dependent manner.
Article in Journal of experimental & clinical cancer research : CR, 2020. 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 32 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
32 citing papers in PubMed, 45 citations in OpenAlex.
- Deciphering the action mechanism of the sacred plant "Ashvattha" (Ficus religiosa L.) in the treatment of delayed-onset muscle soreness.Journal of Ayurveda and integrative medicine · 2026Article
- Wnt/β-catenin signaling in hepatocellular carcinoma: a key player in resistance to targeted and immunotherapies.Carcinogenesis · 2026Review
- Clusterin elaborated by renal tubular epithelial cells under high oxalate stress serves as a matrix protein to facilitate kidney stone formation.Cellular and molecular life sciences : CMLS · 2026Article
- GXYLT2 serves as a prognostic biomarker and is associated with β-catenin activation and gastric cancer aggressiveness.Genes & diseases · 2026Article
- Evidence that extra copies of chromosome 1q play a role in the early phases of pancreatic neoplasia.Science advances · 2026Article
- Traditional Cox regression outperforms large language models in predicting long-term progression of intermediate to advanced hepatocellular carcinoma.Frontiers in oncology · 2026Article
- ZCCHC4 Orchestrates Hepatocellular Carcinoma Metastasis by Regulating Lipid biosynthesis and TMEM97/LCN2/Twist1 Pathway.International journal of biological sciences · 2026Article
- Multifunctional copper-based metal-organic frameworks/chitosan derivative/exosome composite sponge for skin healing.iScience · 2025Article
- Multiple Transcriptome Analyses Reveal the Selected lncRNA-mRNA and circRNA-mRNA Networks in HepG2 Cells Expressing Genotype 4 Swine Hepatitis E Virus ORF3.Veterinary sciences · 2025Article
- Extracellular vesicles-delivered circDB promotes ischemic muscle repair through the miR-34a/USP7/Notch1 signaling pathway.Regenerative therapy · 2025Article
- The prognostic value and functional role of CPSF3 in hepatocellular carcinoma.Scientific reports · 2025Article
- Epithelial to Mesenchymal Transition Transcriptional Regulator ZEB1 in Liver Cancer: Oncogenic Roles and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Telotristat ethyl affects tumour-fibroblast crosstalk in small intestinal neuroendocrine tumours.Journal of neuroendocrinology · 2025Article
- Radiation exposure induces genome-wide alternative splicing events in Aedes aegypti mosquitoes.Scientific reports · 2025Article
- CRTC1 enhances PD-L1-mediated tumor immunosuppression in non-small cell lung cancer via the Notch1/Akt signaling pathway.Frontiers in immunology · 2025Article
- AIBP promotes cell proliferation and migration through the ERK1/2-MAPK signaling pathway in hepatocellular carcinoma.Translational cancer research · 2024Article
- Secretase promotes AD progression: simultaneously cleave Notch and APP.Frontiers in aging neuroscience · 2024Review
- IL-22 signaling promotes sorafenib resistance in hepatocellular carcinoma via STAT3/CD155 signaling axis.Frontiers in immunology · 2024Article
- Unveiling potential drug targets for lung squamous cell carcinoma through the integration of druggable genome and genome-wide association data.Frontiers in genetics · 2024Article
- Comprehensive analysis of skin growth-related hub genes and microenvironment characterization in a mouse expanded skin model.Frontiers in immunology · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHepatocellular carcinoma is the third top cause of cancer-related mortalities worldwide. The prognosis of HCC patients remains poor due to rapid progression and high incidence of tumor recurrence. Nicastrin (NCSTN), a core subunit of γ-Secretase, has been reported to play a vital role in tumor progression. However, no study till now has revealed its role in HCC.
methodsThe expression of NCSTN was evaluated by immunohistochemical staining, Western blot, and quantitative real-time PCR. Cell counting kit-8, colony formation and cell cycle assays were used for evaluating cell growth in vitro. Transwell and wound-healing assays were used for evaluating cell migration and invasion capacity. Immunofluorescence, subcellular protein fractionation and co-immunoprecipitation were used for location analysis of β-catenin. The in vivo functions of NCSTN were illustrated by xenograft tumor models.
resultsNCSTN was dramatically overexpressed in HCC compared to normal liver tissues. Elevated NCSTN expression level was significantly correlated to worse overall and recurrence-free survival of HCC patients. Enhanced NCSTN expression promoted HCC cell growth, migration and invasion in vitro and in vivo. Mechanistic investigations showed that NCSTN induced epithelial-mesenchymal transition (EMT) process via upregulation of Zeb1. Subsequently, we revealed that NCSTN facilitated nuclear translocation of β-catenin, a positive transcriptional regulator of Zeb1. Using Notch and AKT inhibitors, we revealed that NCSTN promoted β-catenin activation through Notch1 and AKT signaling pathway. NCSTN increased AKT and GSK-3β phosphorylation by cleavage of Notch1, which decreased GSK-3β/β-catenin complex. The inactivation of GSK-3β inhibited the β-catenin degradation and promoted nuclear translocation of β-catenin to initiate transcription of Zeb1, resulting in malignant phenotype.
conclusionsOur results demonstrated that NCSTN promoted HCC cell growth and metastasis via β-catenin-mediated upregulation of Zeb1 in a Notch1/AKT dependent manner, suggesting that NCSTN might serve as a potential prognostic marker and therapeutic target for HCC.
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.