ArticleAutophagy2018
Regulation of glycolytic metabolism by autophagy in liver cancer involves selective autophagic degradation of HK2 (hexokinase 2).
Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
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Who cites it
160 citing papers in PubMed, 271 citations in OpenAlex.
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- S100A10 promotes glycolysis and malignant progression of CCA by activating the HK2/ERK signaling pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- The role of e3 ubiquitin ligases and deubiquitinating enzymes in hepatocellular carcinoma.Cell biology and toxicology · 2026Review
- Platycodin D sensitizes head and neck squamous cell carcinoma to cisplatin by inducing autophagy arrest.Oncology reports · 2026Article
- Review
- Deciphering autophagy-metabolism interactions in cancer drug resistance: a comprehensive review.Cancer chemotherapy and pharmacology · 2026Review
- Aryl hydrocarbon receptor impairs HK2-controlled flux of the hexosamine biosynthesis pathway to suppress NETosis in an N-glycosylation-dependent manner.Journal of advanced research · 2026Article
- The Roles of SQSTM1/p62 in Selective Autophagy and Oncogenic Signaling.International journal of molecular sciences · 2026Review
- USP30-mediated Deubiquitination of Hexokinase 2 controls the metabolic fate of glucose and tumor progression.Cell death & disease · 2026Article
- pH-Activatable engineered nanoparticle-based selective hexokinase 2 degrader provokes GSDME-dependent pyroptosis for cancer therapy.Acta pharmaceutica Sinica. B · 2026Article
- Mitophagy in the pathogenesis and management of disease.Cell research · 2026Review
- Article
- SKA3-mediated hypoxia tolerance and metabolic reprogramming promote liver metastasis in lung adenocarcinoma.Cell death & disease · 2025Article
- Urea Transporters in Cancer: Emerging Roles and Their Clinical Implications.Biomedicines · 2025Review
- Regulatory Interplay of p53, AMPK, and mTOR in Decidualization: Implications for Reproductive Competence and Cancer Biology.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- NLRP12 decreases TRIM25-mediated HK2 degradation to promote glycolysis and H3K18la in gastric cancer.Cell death & disease · 2025Article
- Nonhistone lactylation: A hub for tumour metabolic reprogramming and epigenetic regulation.Journal of translational medicine · 2025Review
- Role of the USP family in autophagy regulation and cancer progression.Apoptosis : an international journal on programmed cell death · 2025Review
- Review
100 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Impaired macroautophagy/autophagy and high levels of glycolysis are prevalent in liver cancer. However, it remains unknown whether there is a regulatory relationship between autophagy and glycolytic metabolism. In this study, by utilizing cancer cells with basal or impaired autophagic flux, we demonstrated that glycolytic activity is negatively correlated with autophagy level. The autophagic degradation of HK2 (hexokinase 2), a crucial glycolytic enzyme catalyzing the conversion of glucose to glucose-6-phosphate, was found to be involved in the regulation of glycolysis by autophagy. The Lys63-linked ubiquitination of HK2 catalyzed by the E3 ligase TRAF6 was critical for the subsequent recognition of HK2 by the autophagy receptor protein SQSTM1/p62 for the process of selective autophagic degradation. In a tissue microarray of human liver cancer, the combination of high HK2 expression and high SQSTM1 expression was shown to have biological and prognostic significance. Furthermore, 3-BrPA, a pyruvate analog targeting HK2, significantly decreased the growth of autophagy-impaired tumors in vitro and in vivo (p < 0.05). By demonstrating the regulation of glycolysis by autophagy through the TRAF6- and SQSTM1-mediated ubiquitination system, our study may open an avenue for developing a glycolysis-targeting therapeutic intervention for treatment of autophagy-impaired liver cancer.
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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.