ArticleGut2019
Oncofetal HLF transactivates c-Jun to promote hepatocellular carcinoma development and sorafenib resistance.
Article in Gut, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 148 citations in OpenAlex.
- Molecular biomarkers for diagnosis, prognosis, precision therapy, and immunotherapy in cholangiocarcinoma, cHCC-CCA, and HCC.Hepatology communications · 2026Review
- Genotype-driven variations in lncRNA expression underlie predisposition to high-grade serous ovarian cancer.Journal of advanced research · 2026Article
- Defect-Engineered BiOAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Potential of RAD51C as a hub gene and therapeutic target in bladder cancer: insights from bioinformatics and experimental analysis.International journal of surgery (London, England) · 2026Article
- Oncofetal reprogramming in hepatocellular carcinoma: linking developmental programs to cancer vaccines and immunotherapy.Clinical and molecular hepatology · 2026Review
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- Targeting SPAK suppresses progression and averts an immune exhaustive microenvironment in hepatocellular carcinoma.Nature communications · 2026Article
- Veratramine influences the proliferation of human osteosarcoma cells through modulating the PI3K/AKT signaling cascade.Genes & diseases · 2026Article
- Bmi1 represses HLF to drive the formation and development of intrahepatic cholangiocarcinoma.British journal of cancer · 2026Article
- Article
- Neuro-oncological ventral antigen 1 regulates liver cancer stem cell properties and Lenvatinib resistance via targeting SOX4.Cancer cell international · 2025Article
- HLF transactivatesScience advances · 2025Article
- Differential expression pattern of CC chemokine receptor 7 guides precision treatment of hepatocellular carcinoma.Signal transduction and targeted therapy · 2025Article
- miRNA-338-3p influences the liver cancer stem cells and lenvatinib resistance properties by targeting SOX4.Scientific reports · 2025Article
- Estrogen inhibits hepatocellular carcinoma progression dependent on HOXA11-AS/HOXA11.Translational oncology · 2025Article
- Patient-derived xenograft model: Applications and challenges in liver cancer.Chinese medical journal · 2025Review
- SWI/SNF ATPase silenced HLF potentiates lung metastasis in solid cancers.Nature communications · 2025Article
- HBV sequence integrated to enhancer acting as oncogenic driver epigenetically promotes hepatocellular carcinoma development.Journal of experimental & clinical cancer research : CR · 2025Article
- Article
- microRNA-2117 Negatively Regulates Liver Cancer Stem Cells Expansion and Chemoresistance Via Targeting SOX2.Molecular carcinogenesis · 2025Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aimsThe unique expression pattern makes oncofetal proteins ideal diagnostic biomarkers and therapeutic targets in cancer. However, few oncofetal proteins have been identified and entered clinical practice.
methodsFetal liver, adult liver and hepatocellular carcinoma (HCC) tissues were employed to assess the expression of hepatic leukaemia factor (HLF). The impact of HLF on HCC onset and progression was investigated both in vivo and in vitro. The association between HLF and patient prognosis was determined in patient cohorts. The correlation between HLF expression and sorafenib benefits in HCC was further evaluated in patient cohorts and patient-derived xenografts (PDXs).
resultsHLF is a novel oncofetal protein which is reactivated in HCC by SOX2 and OCT4. Functional studies revealed that HLF transactivates c-Jun to promote tumour initiating cell (TIC) generation and enhances TIC-like properties of hepatoma cells, thus driving HCC initiation and progression. Consistently, our clinical investigations elucidated the association between HLF and patient prognosis and unravelled the close correlation between HLF levels and c-Jun expression in patient HCCs. Importantly, HLF/c-Jun axis determines the responses of hepatoma cells to sorafenib treatment, and interference of HLF abrogated c-Jun activation and enhanced sorafenib response. Analysis of patient cohorts and PDXs further suggests that HLF/c-Jun axis might serve as a biomarker for sorafenib benefits in HCC patients.
conclusionsOur findings uncovered HLF as a novel oncofetal protein and revealed the crucial role of the HLF/c-Jun axis in HCC development and sorafenib response, rendering HLF as an optimal target for the prevention and intervention of 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.