ArticleCell death & disease2020
HIF-1α regulates cellular metabolism, and Imatinib resistance by targeting phosphogluconate dehydrogenase in gastrointestinal stromal tumors.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 32 citations in OpenAlex.
- Molecular classification identifies aggressive gastrointestinal stromal tumor subtype targetable by PARP inhibitors.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- A Review of HIF-1α-Mediated Integration of Metabolic Reprogramming, Mitochondrial Function, and PI3K/Akt-MAPK-Nrf2-NF-κB Signaling.Antioxidants (Basel, Switzerland) · 2026Review
- Targeted Therapy for Advanced Gastrointestinal Stromal Tumors: Evolution and Future Directions.Drug design, development and therapy · 2026Review
- The Mechanisms of Imatinib Resistance in Gastrointestinal Stromal Tumours: Theoretical Basis and Therapeutic Aspect.Journal of cellular and molecular medicine · 2025Review
- ETV1 genetic polymorphisms as a candidate prognosis biomarker of Gastrointestinal stromal tumor.Cancer chemotherapy and pharmacology · 2025Article
- Downregulation of ferroptosis-related Genes can regulate the invasion and migration of osteosarcoma cells.Scientific reports · 2025Article
- The Pentose Phosphate Pathway: From Mechanisms to Implications for Gastrointestinal Cancers.International journal of molecular sciences · 2025Review
- Hypoxia and activation of hypoxia inducible factor alpha as influencers of inflammatory helper T cells in autoimmune disease - a link between cancer and autoimmunity.Frontiers in immunology · 2025Review
- Gene Mutations in Gastrointestinal Stromal Tumors: Advances in Treatment and Mechanism Research.Global medical genetics · 2024Review
- scStateDynamics: deciphering the drug-responsive tumor cell state dynamics by modeling single-cell level expression changes.Genome biology · 2024Article
- Current Drug Resistance Mechanisms and Treatment Options in Gastrointestinal Stromal Tumors: Summary and Update.Current treatment options in oncology · 2024Review
- Promoting reactive oxygen species accumulation to overcome tyrosine kinase inhibitor resistance in cancer.Cancer cell international · 2024Review
- Hypoxia-Inducible Factor 1-Alpha (HIF-1α): An Essential Regulator in Cellular Metabolic Control.Cureus · 2024Review
- Human papillomavirus-16 E6 activates the pentose phosphate pathway to promote cervical cancer cell proliferation by inhibiting G6PD lactylation.Redox biology · 2024Article
- Deciphering the tumor immune microenvironment of imatinib-resistance in advanced gastrointestinal stromal tumors at single-cell resolution.Cell death & disease · 2024Article
- KIT mutations and expression: current knowledge and new insights for overcoming IM resistance in GIST.Cell communication and signaling : CCS · 2024Review
- CRABP2 affects chemotherapy resistance of ovarian cancer by regulating the expression of HIF1α.Cell death & disease · 2024Article
- Review
- ATP13A2 activates the pentose phosphate pathway to promote colorectal cancer growth though TFEB-PGD axis.Clinical and translational medicine · 2023Article
- Metabolomic and transcriptomic response to imatinib treatment of gastrointestinal stromal tumour in xenograft-bearing mice.Translational oncology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pentose phosphate pathway (PPP) plays a critical role in maintaining cellular redox homeostasis in tumor cells and macromolecule biosynthesis. Upregulation of the PPP has been shown in several types of tumor. However, how the PPP is regulated to confer selective growth advantages on drug resistant tumor cells is not well understood. Here we show a metabolic shift from tricarboxylic acid cycle (TCA) to PPP after a long period induction of Imatinib (IM). One of the rate-limiting enzymes of the PPP-phosphogluconate dehydrogenase (PGD), is dramatically upregulated in gastrointestinal stromal tumors (GISTs) and GIST cell lines resistant to Imatinib (IM) compared with sensitive controls. Functional studies revealed that the overexpression of PGD in resistant GIST cell lines promoted cell proliferation and suppressed cell apoptosis. Mechanistic analyses suggested that the protein level of hypoxia inducible factor-1α (HIF-1α) increased during long time stimulation of reactive oxygen species (ROS) produced by IM. Importantly, we further demonstrated that HIF-1α also had positive correlation with PGD, resulting in the change of metabolic pathway, and ultimately causing drug resistance in GIST. Our findings show that long term use of IM alters the metabolic phenotype of GIST through ROS and HIF-1α, and this may contribute to IM resistance. Our work offers preclinical proof of metabolic target as an effective strategy for the treatment of drug resistance in GIST.
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