ArticleOncotarget2015
Hepatitis B virus X protein induces expression of alpha-fetoprotein and activates PI3K/mTOR signaling pathway in liver cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 76 citations in OpenAlex.
- HBx Promotes Liver Cancer Cells to Escape NK-92 Cell Attack by Mediating ADAM10 to Enzyme Cut MICA/B Shedding From Cancer Cell Membrane.Journal of cellular and molecular medicine · 2026Article
- Performance of GAAD and GALAD Biomarker Panels for HCC Detection in Patients with MASLD or ALD Cirrhosis.Cancers · 2025Article
- Insight into the mechanisms regulating liver cancer stem cells by hepatitis B virus X protein.Infectious agents and cancer · 2024Review
- Chinese medicine in the treatment of chronic hepatitis B: The mechanisms of signal pathway regulation.Heliyon · 2024Review
- Alpha-fetoprotein: Past, present, and future.Hepatology communications · 2024Review
- A genetic variant ofJournal of clinical microbiology · 2024Article
- mTOR Signaling: Roles in Hepatitis B Virus Infection and Hepatocellular Carcinoma.International journal of biological sciences · 2024Review
- Long Noncoding RNA H19: A Novel Oncogene in Liver Cancer.Non-coding RNA · 2023Review
- Vincosamide Has a Function for Inhibiting Malignant Behaviors of Hepatocellular Carcinoma Cells.World journal of oncology · 2022Article
- Emerging roles of cancer-testis antigenes, semenogelin 1 and 2, in neoplastic cells.Cell death discovery · 2021Review
- Dairy consumption and hepatocellular carcinoma risk.Annals of translational medicine · 2021Review
- HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression.Journal of experimental & clinical cancer research : CR · 2021Article
- Profibrotic Signaling and HCC Risk during Chronic Viral Hepatitis: Biomarker Development.Journal of clinical medicine · 2021Review
- AFP-Inhibiting Fragments for Drug Delivery: The Promise and Challenges of Targeting Therapeutics to Cancers.Frontiers in cell and developmental biology · 2021Review
- Hematopoietic Cell Kinase (HCK) Is a Player of the Crosstalk Between Hematopoietic Cells and Bone Marrow Niche Through CXCL12/CXCR4 Axis.Frontiers in cell and developmental biology · 2021Article
- Effects of alpha-fetoprotein on the occurrence and progression of hepatocellular carcinoma.Journal of cancer research and clinical oncology · 2020Review
- Hypoxic gene expression in chronic hepatitis B virus infected patients is not observed in state-of-the-art in vitro and mouse infection models.Scientific reports · 2020Article
- Chronic ethanol consumption and HBV induce abnormal lipid metabolism through HBx/SWELL1/arachidonic acid signaling and activate Tregs in HBV-Tg mice.Theranostics · 2020Article
- Silencing of EPCAM suppresses hepatic fibrosis and hepatic stellate cell proliferation in mice with alcoholic hepatitis via the PI3K/Akt/mTOR signaling pathway.Cell cycle (Georgetown, Tex.) · 2019Article
- Hepatitis B virus X protein (HBx) enhances centrosomal P4.1-associated protein (CPAP) expression to promote hepatocarcinogenesis.Journal of biomedical science · 2019Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
The hepatitis B virus (HBV)-X protein (HBx) induces malignant transformation of liver cells, and elevated expression of alpha-fetoprotein (AFP) is a significant biomarker of hepatocarcinogenesis. However, the role of AFP in HBV-related hepatocarcinogenesis is unclear. In this study, we investigated the regulatory impact of AFP expression on HBx-mediated malignant transformation of human hepatocytes. We found that HBV induced the expression of AFP before that of oncogenes, e.g., Src, Ras and chemokine (C-X-C motif) receptor 4 (CXCR4), and AFP activated protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in HBV-related HCC tissues and in human liver cells transfected with HBx. Cytoplasmic AFP interacted with and inhibited phosphatase and tensin homolog deleted on chromosome 10 (PTEN), activating the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway and promoting mTOR-mediated stimulation of the transcription factor hypoxia inducible factor-1α (HIF-1α), and therefore led to the activation of the promoters of Src, CXCR4, and Ras genes. On the contrary, reduced expression of AFP by siRNA resulted in the repression of p-mTOR, pAKT, Src, CXCR4, and Ras in human malignant liver cells. Taken together, for the first time our study indicates that HBx-induced AFP expression critically promote malignant transformation in liver cells through the activation of PI3K/mTOR signaling.
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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.