ArticleEBioMedicine2020
Tonicity-responsive enhancer-binding protein promotes stemness of liver cancer and cisplatin resistance.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- LncRNA NRAV is associated with unfavorable prognosis and immune-related transcriptional features in hepatocellular carcinoma.Discover oncology · 2026Article
- Hepatocyte TonEBP promotes metabolic stress-induced hepatic fibroinflammation involving transcriptional activation of ELR⁺ CXC chemokines.Cell death discovery · 2026Article
- PFDN6L Gene Predicts Good Prognosis Associated with Its Inhibition of the Stem-Ness Properties in Hepatocellular Carcinoma.Oncology research · 2025Article
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- Nuclear Factor of Activated T Cells (NFAT) Proteins as Targeted Molecules in Diseases: A Narrative Review.Cureus · 2024Review
- Screening and molecular docking verification of feature genes related to phospholipid metabolism in hepatocarcinoma caused by hepatitis B.Lipids in health and disease · 2024Article
- ALDH2 dysfunction and alcohol cooperate in cancer stem cell enrichment.Carcinogenesis · 2024Article
- Breaking the Barriers of Therapy Resistance: Harnessing Ferroptosis for Effective Hepatocellular Carcinoma Therapy.Journal of hepatocellular carcinoma · 2024Review
- Chemotherapeutic Drug-Regulated Cytokines Might Influence Therapeutic Efficacy in HCC.International journal of molecular sciences · 2021Review
- Epigenetic Regulator KDM4D Restricts TumorigenesisFrontiers in oncology · 2021Article
- GRK2 deletion improves the function of skin flap following ischemia-reperfusion injury by regulating Drp1.American journal of translational research · 2021Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHigh recurrence and chemoresistance drive the high mortality in hepatocellular carcinoma (HCC). Although cancer stem cells are considered to be the source of recurrent and chemoresistant tumors, they remain poorly defined in HCC. Tonicity-responsive enhancer binding protein (TonEBP) is elevated in almost all HCC tumors and associated with recurrence and death. We aimed to identify function of TonEBP in stemness and chemoresistance of liver cancer.
methodsTumors obtained from 280 HCC patients were analyzed by immunohistochemical analyses. Stemness and chemoresistance of liver CSCs (LCSCs) were investigated using cell culture. Tumor-initiating activity was measured by implanting LCSCs into BALB/c nude mice.
findingsExpression of TonEBP is higher in LCSCs in HCC cell lines and correlated with markers of LCSCs whose expression is significantly associated with poor prognosis of HCC patients. TonEBP mediates ATM-mediated activation of NF-κB, which stimulates the promoter of a key stem cell transcription factor SOX2. As expected, TonEBP is required for the tumorigenesis and self-renewal of LSCSs. Cisplatin induces the recruitment of the ERCC1/XPF dimer to the chromatin in a TonEBP-dependent manner leading to DNA repair and cisplatin resistance. The cisplatin-induced inflammation in LSCSs is also dependent on the TonEBP-ERCC1/XPF complex, and leads to enhanced stemness via the ATM-NF-κB-SOX2 pathway. In HCC patients, tumor expression of ERCC1/XPF predicts recurrence and death in a TonEBP-dependent manner.
interpretationTonEBP promotes stemness and cisplatin resistance of HCC via ATM-NF-κB. TonEBP is a key regulator of LCSCs and a promising therapeutic target for HCC and its recurrence.
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