ArticleJournal of translational medicine2022
VCP interaction with HMGB1 promotes hepatocellular carcinoma progression by activating the PI3K/AKT/mTOR pathway.
Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 45 citations in OpenAlex.
- VCP at the crossroads of UPS and autophagy in cancer.Genes & diseases · 2027Review
- Multi-omics analysis identifies CKLF as a promoter for HCC progression by regulating the AKT, ERK pathways, and infiltrating immune cells.Translational oncology · 2026Article
- Plexin A2 regulated the metastasis in breast cancer through MCM7.BMC cancer · 2026Article
- CCDC137 affects sorafenib resistance in hepatocellular carcinoma cells by activating the AKT/mTOR signaling pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- E3 Ligases and Deubiquitinases in Controlling High-Mobility Group Box (HMGB) Protein Functions.International journal of molecular sciences · 2026Review
- Quantitative Proteomics Unveils Comprehensive Tissue-Specific VCP Interaction Networks in Mice.Scientific data · 2026Article
- Prognostic Genes Linked to Asparagine Metabolism in Hepatocellular Carcinoma: Identification, Validation, and Regulatory Mechanisms Based on Transcriptome and Single-Cell RNA Sequencing.International journal of molecular sciences · 2026Article
- Valosin-Containing Protein (VCP)/p97 Expression Correlation of Prognosis of Clear Cell Renal Cell Carcinomas.Biomedicines · 2026Article
- Evaluation of Tissue Expression of HMBG1 Protein in Patients With Breast Cancer.European journal of breast health · 2025Article
- VCP Promotes Cholangiocarcinoma Development by Mediating BAP1 Ubiquitination-Dependent Degradation.Cancer science · 2025Article
- Unraveling the complex role of tumor-associated neutrophils within solid tumors.Cancer immunology, immunotherapy : CII · 2025Review
- Decoding Hepatocellular Carcinoma Metastasis: Molecular Mechanisms, Targeted Therapies, and Potential Biomarkers.Current issues in molecular biology · 2025Review
- Review
- VCP downstream metabolite glycerol-3-phosphate (G3P) inhibits CD8Signal transduction and targeted therapy · 2025Article
- Sialylated Immunoglobulin G Promotes the Malignant Progression of Oral Squamous Cell Carcinoma through VCP-Mediated NDUFB6 Stabilization Regulated Mitochondrial Oxidative Phosphorylation.Research (Washington, D.C.) · 2025Article
- IL-1β-Stimulated Bone Mesenchymal Stem Cell-Derived Exosomes Mitigate Sepsis through Modulation of HMGB1/AKT Pathway and M2 Macrophage Polarization.Current molecular medicine · 2025Article
- CNDP1 Suppresses the Malignant Behavior of Hepatoma CellCurrent cancer drug targets · 2025Article
- LncRNA FTX accelerates the progression of hepatocellular carcinoma by FTX/miR-374a-3p/HMGB1 pathway.International journal of medical sciences · 2025Article
- Single-cell sequencing reveals the role of aggrephagy-related patterns in tumor microenvironment, prognosis and immunotherapy in endometrial cancer.Frontiers in oncology · 2025Article
- PFDN6L Gene Predicts Good Prognosis Associated with Its Inhibition of the Stem-Ness Properties in Hepatocellular Carcinoma.Oncology research · 2025Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) is the most common pathological type of liver cancer. Valosin-containing protein (VCP) is a member of the AAA-ATPase family associated with multiple molecular functions and involved in tumor metastasis and prognosis. However, the role of VCP in HCC progression is still unclear.
methodsWe examined the expression of VCP in HCC using the RNA sequencing and microarray data from public databases and measured it in clinical samples and cell lines by western blot, and immunohistochemistry (IHC). We also evaluated the correlation between VCP and clinical features. The VCP-interacting proteins were identified by co-immunoprecipitation combined with mass spectrometry (CoIP/MS). The underlying molecular mechanisms were investigated using in vitro and in vivo models of HCC.
resultsWe found that VCP expression is significantly increased in tumor tissues and is associated with advanced TNM stages and poorer prognosis in HCC patients. In vitro analyses revealed that VCP overexpression promoted HCC cell proliferation, migration, and invasion via PI3K/AKT/mTOR pathway activation. Conversely, VCP knockdown resulted in the reverse phenotypes. In vivo studies indicated that up-regulated VCP expression accelerated tumor growth in a subcutaneous HCC model. The D1 domain of VCP and A box of HMGB1 were identified as the critical regions for their interaction, and D1 area was required for the tumor-promoting effects induced by VCP expression. VCP enhanced the protein stability of HMGB1 by decreasing its degradation via ubiquitin-proteasome process. Inhibition of HMGB1 markedly attenuated VCP-mediated HCC progression and downstream activation of PI3K/AKT/mTOR signals.
conclusionCollectively, these findings demonstrate that VCP is a potential prognostic biomarker in HCC and exhibits oncogenic roles via PI3K/AKT/mTOR pathway activation. HMGB1 played an essential role in VCP-mediated HCC progression, indicating that VCP and HMGB1 are potential therapeutic targets in human HCC.
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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.