ArticleHepatology (Baltimore, Md.)2015
Axl activates autocrine transforming growth factor-β signaling in hepatocellular carcinoma.
Article in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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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.
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Who cites it
94 citing papers in PubMed, 153 citations in OpenAlex.
- A Phase I/II Multicenter Study of Single-Agent Foretinib as First-Line Therapy in Patients with Advanced Hepatocellular Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- A phase 1b, multicentre, dose escalation, safety and pharmacokinetics study of tilvestamab (BGB149) in relapsed, platinum-resistant, high-grade serous ovarian cancer (PROC) patients.British journal of cancer · 2025Article
- Sex hormone-binding globulin restrains hepatic fibrosis via inhibition of Tgfβ expression.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Inhibition of the Caveolin-1 pathway promotes apoptosis and overcomes pan-tyrosine kinase inhibitor resistance in hepatocellular carcinoma.Cell death & disease · 2025Article
- Benzaldehyde suppresses epithelial-mesenchymal plasticity and overcomes treatment resistance in cancer by targeting the interaction of 14-3-3ζ with H3S28ph.British journal of cancer · 2025Article
- Antitumor activity of gilteritinib, an inhibitor of AXL, in human solid tumors.Cell death discovery · 2025Article
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- Dual Roles of microRNA-122 in Hepatocellular Carcinoma and Breast Cancer Progression and Metastasis: A Comprehensive Review.Current issues in molecular biology · 2024Review
- CD73 promotes non-small cell lung cancer metastasis by regulating Axl signaling independent of GAS6.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Anti-PD-L1 antibodies promote cellular proliferation by activating the PD-L1-AXL signal relay in liver cancer cells.Hepatology international · 2024Article
- The Combined Use of Dickkopf-1 and Soluble Axl Improves Hepatocellular Carcinoma Diagnostic Efficacy in Hepatitis C Patients.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Tumor-Extrinsic Axl Expression Shapes an Inflammatory Microenvironment Independent of Tumor Cell Promoting Axl Signaling in Hepatocellular Carcinoma.International journal of molecular sciences · 2024Article
- Therapeutic targeting of the functionally elusive TAM receptor family.Nature reviews. Drug discovery · 2024Review
- Targeting AXL induces tumor-intrinsic immunogenic response in tyrosine kinase inhibitor-resistant liver cancer.Cell death & disease · 2024Article
- GAS6/TAM Axis as Therapeutic Target in Liver Diseases.Seminars in liver disease · 2024Article
- Article
- From MASH to HCC: the role of Gas6/TAM receptors.Frontiers in immunology · 2024Review
- KHDRBS3 accelerates glycolysis and promotes malignancy of hepatocellular carcinoma via upregulating 14-3-3ζ.Cancer cell international · 2023Article
- Gas6 in chronic liver disease-a novel blood-based biomarker for liver fibrosis.Cell death discovery · 2023Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledIn hepatocellular carcinoma (HCC), intrahepatic metastasis frequently correlates with epithelial to mesenchymal transition (EMT) of malignant hepatocytes. Several mechanisms have been identified to be essentially involved in hepatocellular EMT, among them transforming growth factor (TGF)-β signaling. Here we show the up-regulation and activation of the receptor tyrosine kinase Axl in EMT-transformed hepatoma cells. Knockdown of Axl expression resulted in abrogation of invasive and transendothelial migratory abilities of mesenchymal HCC cells in vitro and Axl overexpression-induced metastatic colonization of epithelial hepatoma cells in vivo. Importantly, Axl knockdown severely impaired resistance to TGF-β-mediated growth inhibition. Analysis of the Axl interactome revealed binding of Axl to 14-3-3ζ, which is essentially required for Axl-mediated cell invasion, transendothelial migration, and resistance against TGF-β. Axl/14-3-3ζ signaling caused phosphorylation of Smad3 linker region (Smad3L) at Ser213, resulting in the up-regulation of tumor-progressive TGF-β target genes such as PAI1, MMP9, and Snail as well as augmented TGF-β1 secretion in mesenchymal HCC cells. Accordingly, high Axl expression in HCC patient samples correlated with elevated vessel invasion of HCC cells, higher risk of tumor recurrence after liver transplantation, strong phosphorylation of Smad3L, and lower survival. In addition, elevated expression of both Axl and 14-3-3ζ showed strongly reduced survival of HCC patients.
conclusionOur data suggest that Axl/14-3-3ζ signaling is central for TGF-β-mediated HCC progression and a promising target for HCC therapy.
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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.