ArticleHepatology (Baltimore, Md.)2008
Hepatocellular cancer arises from loss of transforming growth factor beta signaling adaptor protein embryonic liver fodrin through abnormal angiogenesis.
Article in Hepatology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 68 citations in OpenAlex.
- Synergistic Effects of Radiotherapy and PD‑1 Blockade in a Human‑Mimetic BRCAness Model of Triple-Negative Breast Cancer.International journal of biological sciences · 2025Article
- Mechanistically based blood proteomic markers in the TGF-β pathway stratify risk of hepatocellular cancer in patients with cirrhosis.Genes & cancer · 2024Article
- SMAD Proteins in TGF-β Signalling Pathway in Cancer: Regulatory Mechanisms and Clinical Applications.Diagnostics (Basel, Switzerland) · 2023Review
- Direct and Indirect Effect of TGFβ on Treg Transendothelial Recruitment in HCC Tissue Microenvironment.International journal of molecular sciences · 2021Article
- TGF-β Signaling in Liver, Pancreas, and Gastrointestinal Diseases and Cancer.Gastroenterology · 2021Review
- βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases.International journal of biological sciences · 2021Review
- Targeting Liver Cancer Stem Cells: An Alternative Therapeutic Approach for Liver Cancer.Cancers · 2020Review
- A Fresh Look at the Structure, Regulation, and Functions of Fodrin.Molecular and cellular biology · 2020Review
- Article
- Maternal Consumption of a Low-Isoflavone Soy Protein Isolate Diet Accelerates Chemically Induced Hepatic Carcinogenesis in Male Rat Offspring.Nutrients · 2020Article
- Validation of Hepatocellular Carcinoma Experimental Models for TGF-β Promoting Tumor Progression.Cancers · 2019Review
- Endoglin-targeted contrast-enhanced ultrasound imaging in hepatoblastoma xenografts.Oncology letters · 2018Article
- β2 spectrin-mediated differentiation repressed the properties of liver cancer stem cells through β-catenin.Cell death & disease · 2018Article
- The role of βII spectrin in cardiac health and disease.Life sciences · 2018Review
- Inhibition of Estrogen Signaling Reduces the Incidence ofInternational journal of biological sciences · 2018Article
- IL6-mediated inflammatory loop reprograms normal to epithelial-mesenchymal transitionHepatology (Baltimore, Md.) · 2017Article
- CHK2 is involved in the p53-independent radiosensitizing effects of valproic acid.Oncology letters · 2017Article
- TGF-β signaling in liver and gastrointestinal cancers.Cancer letters · 2016Review
- Caspase-3/7-mediated Cleavage of β2-spectrin is Required for Acetaminophen-induced Liver Damage.International journal of biological sciences · 2016Article
- Apoptosis in liver carcinogenesis and chemotherapy.Hepatic oncology · 2015Review
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
unlabelledWe have previously demonstrated that 40%-70% of elf(+/-) mice spontaneously develop hepatocellular cancer (HCC) within 15 months, revealing the importance of the transforming growth factor-beta (TGF-beta) signaling pathway in suppressing tumorigenesis in the liver. The current study was carried out to investigate mechanisms by which embryonic liver fodrin (ELF), a crucial Smad3/4 adaptor, suppresses liver tumor formation. Histological analysis of hyperplastic liver tissues from elf(+/-) mice revealed abundant newly formed vascular structures, suggesting aberrant angiogenesis with loss of ELF function. In addition, elf(+/-) mice displayed an expansion of endothelial progenitor cells. Ectopic ELF expression in fetal bovine heart endothelial (FBHE) cells resulted in cell cycle arrest and apoptosis. Further analysis of developing yolk sacs of elf(-/-) mice revealed a failure of normal vasculature and significantly decreased endothelial cell differentiation with embryonic lethality. Immunohistochemical analysis of hepatocellular cancer (HCC) from the elf(+/-) mice revealed an abnormal angiogenic profile, suggesting the role of ELF as an angiogenic regulator in suppressing HCC. Lastly, acute small interfering RNA (siRNA) inhibition of ELF raised retinoblastoma protein (pRb) levels nearly fourfold in HepG2 cells (a hepatocellular carcinoma cell line) as well as in cow pulmonary artery endothelial (CPAE) cells, respectively.
conclusionTaken together these results, ELF, a TGF-beta adaptor and signaling molecule, functions as a critical adaptor protein in TGF-beta modulation of angiogenesis as well as cell cycle progression. Loss of ELF in the liver leads the cancer formation by deregulated hepatocyte proliferation and stimulation of angiogenesis in early cancers. Our studies propose that ELF is potentially a powerful target for mimetics enhancing the TGF-beta pathway tumor suppression of HCC.
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