ArticleCell death & disease2021
Reciprocal regulation of LOXL2 and HIF1α drives the Warburg effect to support pancreatic cancer aggressiveness.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- The prediction value of LOXL-2 in the clinical pathology and prognosis of cancers: A meta-analysis and bioinformatics analysis.Scientific reports · 2025Pooled it
- Detection of Pancreatic Cancer via Specific Metabolite Markers: A Metabolomics Approach.Health science reports · 2026Article
- Lysyl oxidase (LOX) family proteins in extracellular matrix homeostasis: roles in disease and radiation-induced pathogenesis.Molecular biology reports · 2026Review
- The central regulator HIF-1α in digestive system pathologies: inflammation and cancer.Frontiers in immunology · 2026Review
- ITGA3 promotes pancreatic cancer progression through HIF1α- and c-Myc-driven glycolysis in a collagen I-dependent autocrine manner.Cancer gene therapy · 2025Article
- Reprogramming of glucose metabolism in pancreatic cancer: mechanisms, implications, and therapeutic perspectives.Frontiers in immunology · 2025Review
- PARP9 drives the malignant progression of pancreatic cancer cells by regulating apoptosis, DNA damage, and multidrug efflux systems.Frontiers in cell and developmental biology · 2025Article
- ETV4 interacts with LOXL2 to induce epigenetic activation of NID1 during colorectal cancer progression.International journal of biological sciences · 2025Article
- LOXL2 inhibition ameliorates pulmonary artery remodeling in pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Skeletal Muscle SIRT3 Deficiency Contributes to Pulmonary Vascular Remodeling in Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction.Circulation · 2024Article
- A Comprehensive Review of Protein Biomarkers for Invasive Lung Cancer.Current oncology (Toronto, Ont.) · 2024Review
- Exploring the Role of Desmoplastic Physical Stroma in Pancreatic Cancer Progression Using a Three-Dimensional Collagen Matrix Model.Bioengineering (Basel, Switzerland) · 2023Article
- LOXL2 in Cancer: A Two-Decade Perspective.International journal of molecular sciences · 2023Review
- Lysyl Oxidases as Targets for Cancer Therapy and Diagnostic Imaging.ChemMedChem · 2023Review
- PYGL-mediated glucose metabolism reprogramming promotes EMT phenotype and metastasis of pancreatic cancer.International journal of biological sciences · 2023Article
- Context Matters: Response Heterogeneity to Collagen-Targeting Approaches in Desmoplastic Cancers.Cancers · 2022Review
- Hypoxia Alters the Proteome Profile and Enhances the Angiogenic Potential of Dental Pulp Stem Cell-Derived Exosomes.Biomolecules · 2022Article
- A Novel Small-Molecule Inhibitor of SREBP-1 Based on Natural Product Monomers Upregulates the Sensitivity of Lung Squamous Cell Carcinoma Cells to Antitumor Drugs.Frontiers in pharmacology · 2022Article
- A novel epithelial-mesenchymal transition (EMT)-related gene signature of predictive value for the survival outcomes in lung adenocarcinoma.Frontiers in oncology · 2022Article
- Hypoxia activates the unfolded protein response signaling network: An adaptive mechanism for endometriosis.Frontiers in endocrinology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxic microenvironment is common in solid tumors, particularly in pancreatic ductal adenocarcinoma (PDAC). The Warburg effect is known to facilitate cancer aggressiveness and has long been linked to hypoxia, yet the underlying mechanism remains largely unknown. In this study, we identify that lysyl oxidase-like 2 (LOXL2) is a hypoxia-responsive gene and is essential for the Warburg effect in PDAC. LOXL2 stabilizes hypoxia-inducible factor 1α (HIF1α) from prolyl hydroxylase (PHD)-dependent hydroxylation via hydrogen peroxide generation, thereby facilitating the transcription of multiple glycolytic genes. Therefore, a positive feedback loop exists between LOXL2 and HIF1α that facilitates glycolytic metabolism under hypoxia. Moreover, LOXL2 couples the Warburg effect to tumor growth and metastasis in PDAC. Hijacking glycolysis largely compromises LOXL2-induced oncogenic activities. Collectively, our results identify a hitherto unknown hypoxia-LOXL2-HIF1α axis in regulating the Warburg effect and provide an intriguing drug target for PDAC therapy.
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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.