ArticleCell death & disease2023
Hexokinase 2 confers radio-resistance in hepatocellular carcinoma by promoting autophagy-dependent degradation of AIMP2.
Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Oral of PtCuS nanoclusters mitigates acute radiation-induced intestinal injury by coordinating glutathione metabolism, macrophage repolarization, and gut microbiota.Materials today. Bio · 2026Article
- Review
- Research progress and therapeutic strategies in hepatocellular carcinoma metabolic reprogramming.Journal of advanced research · 2026Review
- Metabolic Vulnerabilities as a Therapeutic Target in Breast Cancer.Current oncology (Toronto, Ont.) · 2026Review
- Targeting Glycolytic Metabolism in Cancer Therapy: Current Approaches and Future Perspectives.Cells · 2026Review
- Article
- Targeting SRC/STAT3 Signaling Impairs Cancer Stem Cell Activity by Downregulation of Hexokinase-2 in Radioresistant Triple-Negative Breast Cancer Cells.Oncology research · 2026Article
- IGF2BP1 orchestrates glycolytic reprogramming via HK2 to accelerate hepatocellular carcinoma malignancy.American journal of cancer research · 2026Article
- Review
- RNASEH2C enhances TRAF3IP1 to degrade RAI14 in lysosomes thus hindering macrophage antigen presentation and advancing liver cancer.Cell death & disease · 2025Article
- Demethoxycurcumin suppresses HK2-mediated glycolysis by targeting PTEN/Akt signaling.Cancer gene therapy · 2025Article
- Advancements in research on the role of the key glycolytic enzyme hexokinase 2 in the regulation of tumor immune evasion (Review).Oncology letters · 2025Review
- Hexokinase 2 is an RNA-binding protein that regulates mRNA translation independently of glycolysis and induces melanoma cell proliferation.PLoS biology · 2025Article
- AttBiomarker: unveiling preeclampsia biomarkers and molecular pathways through two-stage gene selection techniques and attention-based CNN with gene regulatory network analysis.Briefings in bioinformatics · 2025Article
- A CCR5 antagonist enhances the radiosensitivity of hepatocarcinoma in a mouse model.Journal of radiation research · 2025Article
- Foot-and-mouth disease virus activates glycolysis and hijacks HK2 to inhibit innate immunity and promote viral replication.Veterinary research · 2025Article
- [High expression of hexokinase 2 promotes proliferation, migration and invasion of colorectal cancer cells by activating the JAK/STAT pathway and regulating tumor immune microenvironment].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Radioresistance in Hepatocellular Carcinoma: Biological Bases and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Autophagy-based therapy for hepatocellular carcinoma: from standard treatments to combination therapy, oncolytic virotherapy, and targeted nanomedicines.Clinical and experimental medicine · 2024Review
- MTCH2 promotes the malignant progression of ovarian cancer through the upregulation of AIMP2 expression levels, mitochondrial dysfunction and by mediating energy metabolism.Oncology letters · 2024Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
With technological advancements, radiotherapy (RT) has become an effective non-surgical treatment for hepatocellular carcinoma (HCC), comprehensively improving the local control rate of patients with HCC. However, some patients with HCC still experience radio-resistance, cancer recurrence, and distant metastasis following RT. Our previous study has revealed that hexokinase 2 (HK2), a potent oncogene, was overexpressed in radio-resistant HCC cell lines; however, its role in HCC radio-resistance remains elusive. Here, we confirmed the upregulation of HK2 in HCC tissue, which is related to unfavorable prognosis in patients with HCC, and demonstrated that HK2 exerts a radio-resistant role by attenuating apoptosis and promoting proliferation in HCC cell lines. HK2 downregulation combined with ionizing radiation showed an excellent synergistic lethal effect. Mechanistically, HK2 alleviated ionizing radiation-mediated apoptosis by complexing with pro-apoptotic protein aminoacyl tRNA synthetase complex interacting multifunctional protein 2 (AIMP2) while enhancing its autophagic lysosomal-dependent degradation, thereby increasing radio-resistance of HCC. Pharmacologically, ketoconazole, an FDA-approved antifungal drug, served as an inhibitor of HK2 and synergistically enhanced the efficacy of RT. Our results indicated that HK2 played a vital role in radio-resistance and could be a potential therapeutic target for improving RT efficacy in HCC.
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