ArticleCancer discovery2013
Hypoxia-dependent modification of collagen networks promotes sarcoma metastasis.
Article in Cancer discovery, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
192 citing papers in PubMed, 1 synthesis or guideline pooled it, 289 citations in OpenAlex.
- Prognostic and Clinicopathological Significance of Hypoxia-Inducible Factor-1α in Endometrial Cancer: A Meta-Analysis.Frontiers in oncology · 2020Pooled it
- Prospective exploratory pilot study of 18 F-FMISO PET/CT for assessing tumor hypoxia in soft tissue sarcomas.Cancer imaging : the official publication of the International Cancer Imaging Society · 2026Trial
- Histopathological Response After Neoadjuvant Chemotherapy for High-Risk Soft-Tissue Sarcomas: A Secondary Analysis of a Randomized Clinical Trial.JAMA network open · 2025Trial
- L-leucine-incorporated 3D-printed SilMA hydrogel scaffolds promote calvarial defect repair with PLOD2-associated collagen remodeling.Materials today. Bio · 2026Article
- Review
- EMILIN-1 in the tumor microenvironment: insights from CNS tumors and beyond.Frontiers in oncology · 2026Review
- Hypoxia-driven metastatic progression in synovial sarcoma: insights from SYO-1 and SW982 models.BMC cancer · 2025Article
- Collagen-disrupting attIL12 TIL therapy boosts deep T cell infiltration via dual signaling activation and CCKAR reduction in sarcomas.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting collagen in "armored and cold" tumors: Overcoming barriers to cancer therapy.Cancer pathogenesis and therapy · 2025Review
- Hypoxic stimulation of DCLK1 transcription and alternative-promoter switching fuels tumor malignancy in clear cell renal cell carcinoma.Cell death & disease · 2025Article
- Structural basis of collagen glucosyltransferase function and its serendipitous role in kojibiose synthesis.Nature communications · 2025Article
- MicroRNA-1303 in cancer pathogenesis and therapy: clinical implications for biomarker development and targeted treatment strategies.Cancer cell international · 2025Review
- Histological Grade, Tumor Breadth, and Hypertension Predict Early Recurrence in Pediatric Sarcoma: A LASSO-Regularized Micro-Cohort Study.Children (Basel, Switzerland) · 2025Article
- Core-Shell Hydrogels with Tunable Stiffness for Breast Cancer Tissue Modelling in an Organ-on-Chip System.Gels (Basel, Switzerland) · 2025Article
- Lysyl hydroxylase 2 glucosylates collagen VI to drive lung cancer progression.The Journal of clinical investigation · 2025Article
- Hypoxia-induced ATF3 escalates breast cancer invasion by increasing collagen deposition via P4HA1.Cell death & disease · 2025Article
- CKAP4 and PLOD2 as novel prognostic biomarkers in hepatocellular carcinoma: a proteomics-driven risk stratification model.Frontiers in cell and developmental biology · 2025Article
- Rational design matrix materials for organoid development and application in biomedicine.Regenerative biomaterials · 2025Review
- Discovery of Glucose Metabolism-Associated Genes in Neuropathic Pain: Insights from Bioinformatics.International journal of molecular sciences · 2024Article
- Article
132 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
unlabelledIntratumoral hypoxia and expression of hypoxia-inducible factor-1α (HIF-1α) correlate with metastasis and poor survival in patients with sarcoma. We show here that hypoxia controls sarcoma metastasis through a novel mechanism wherein HIF-1α enhances expression of the intracellular enzyme procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2). We show that loss of HIF-1α or PLOD2 expression disrupts collagen modification, cell migration, and pulmonary metastasis (but not primary tumor growth) in allograft and autochthonous LSL-Kras(G12D/+); Trp53(fl/fl) murine sarcoma models. Furthermore, ectopic PLOD2 expression restores migration and metastatic potential in HIF-1α-deficient tumors, and analysis of human sarcomas reveals elevated HIF1A and PLOD2 expression in metastatic primary lesions. Pharmacologic inhibition of PLOD enzymatic activity suppresses metastases. Collectively, these data indicate that HIF-1α controls sarcoma metastasis through PLOD2-dependent collagen modification and organization in primary tumors. We conclude that PLOD2 is a novel therapeutic target in sarcomas and successful inhibition of this enzyme may reduce tumor cell dissemination. SIGNIFICANCE: Undifferentiated pleomorphic sarcoma (UPS) is a commonly diagnosed and particularly aggressive sarcoma subtype in adults, which frequently and fatally metastasizes to the lung. Here, we show the potential use of a novel therapeutic target for the treatment of metastatic UPS, specifi cally the collagen-modifying enzyme PLOD2.
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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.