ArticleCancer science2020
Hypoxia-inducible hexokinase-2 enhances anti-apoptotic function via activating autophagy in multiple myeloma.
Article in Cancer science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 55 citations in OpenAlex.
- Regulation of autophagy by the p53 family and the implications for cancer therapies.Discover oncology · 2026Review
- Extracellular Enolase-1 Promotes CAF-Associated Stromal Reprogramming via the Plasmin/TGF-β Axis in Multiple Myeloma.Cancers · 2026Article
- Whole-body periodic acceleration: a new countermeasure against bone loss induced by long-term hindlimb unloading.European journal of applied physiology · 2026Article
- MMSA-1 is regulated by Wnt/TCF4 and involved in multiple myeloma progression and invasion via RAS/RAF signaling pathway.Annals of hematology · 2026Article
- Unraveling autophagy-metabolism crosstalk in cancer: Molecular insights and therapeutic strategies.Theranostics · 2026Review
- Epstein-Barr virus-transformed B-cells from a hypoxia model of the germinal center requires external unsaturated fatty acids.PLoS pathogens · 2025Article
- Article
- Foot-and-mouth disease virus activates glycolysis and hijacks HK2 to inhibit innate immunity and promote viral replication.Veterinary research · 2025Article
- Leveraging a disulfidptosis-based signature to characterize heterogeneity and optimize treatment in multiple myeloma.Frontiers in immunology · 2025Article
- Lactate and Lactylation: Dual Regulators of T-Cell-Mediated Tumor Immunity and Immunotherapy.Biomolecules · 2024Review
- Ubiquitination regulates autophagy in cancer: simple modifications, promising targets.Journal of translational medicine · 2024Review
- Design, Synthesis, and Evaluation of Doxifluridine Derivatives as Nitroreductase-Responsive Anticancer Prodrugs.Molecules (Basel, Switzerland) · 2024Article
- Transcriptional regulation and post-translational modifications in the glycolytic pathway for targeted cancer therapy.Acta pharmacologica Sinica · 2024Review
- The regulatory roles and clinical significance of glycolysis in tumor.Cancer communications (London, England) · 2024Review
- Genetically programmable cell membrane-camouflaged nanoparticles for targeted combination therapy of colorectal cancer.Signal transduction and targeted therapy · 2024Article
- Transcriptional Responses of Different Brain Cell Types to Oxygen Decline.Brain sciences · 2024Article
- The HIF transcription network exerts innate antiviral activity in neurons and limits brain inflammation.Cell reports · 2024Article
- Unraveling the complexity of drug resistance mechanisms to SINE, T cell-engaging therapies and CELMoDs in multiple myeloma: a comprehensive review.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- The Promoting Role of HK II in Tumor Development and the Research Progress of Its Inhibitors.Molecules (Basel, Switzerland) · 2023Review
- Study of Transcriptomic Analysis of Yak (Animals : an open access journal from MDPI · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Multiple myeloma (MM) is an incurable hematopoietic neoplasm derived from plasma cells, and existing in the bone marrow. Recent developments in the field of myeloma onco-biology have enabled the use of proteasome inhibitors (PIs) as key drugs for MM. PIs can increase cell sensitivity to endoplasmic reticulum stress, leading to apoptosis of myeloma cells. PI cannot kill all myeloma cells, however; one reason of this might be activation of autophagy via hypoxic stress in the bone marrow microenvironment. Hypoxia-inducible gene(s) that regulate autophagy may be novel therapeutic target(s) for PI-resistant myeloma cells. Here, a hypoxia-inducible glycolytic enzyme hexokinase-2 (HK2) was demonstrated to contribute by autophagy activation to the acquisition of an anti-apoptotic phenotype in myeloma cells. We found that hypoxic stress led to autophagy activation accompanied by HK2 upregulation in myeloma cells. Under hypoxic conditions, HK2 knockdown inhibited glycolysis and impaired autophagy, inducing apoptosis. The cooperative effects of a PI (bortezomib) against immunodeficient mice inoculated with HK2-knocked down myeloma cells were examined and significant tumor reduction was observed. An HK2 inhibitor, 3-bromopyruvate (3-BrPA), also induced apoptosis under hypoxic rather than normoxic conditions. Further examination of the cooperative effects between 3-BrPA and bortezomib on myeloma cells revealed a significant increase in apoptotic myeloma cells. These results strongly suggested that HK2 regulates the activation of autophagy in hypoxic myeloma cells. Cooperative treatment using PI against a dominant fraction, and HK2 inhibitor against a minor fraction, adapted to the bone marrow microenvironment, may lead to deeper remission for refractory MM.
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