ArticleThe Journal of biological chemistry2010
The lysyl oxidases LOX and LOXL2 are necessary and sufficient to repress E-cadherin in hypoxia: insights into cellular transformation processes mediated by HIF-1.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 2 of them syntheses that pooled it.
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Who cites it
143 citing papers in PubMed, 2 syntheses or guidelines pooled it, 248 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
- Non-hepatic tumors change the activity of genes encoding copper trafficking proteins in the liver.Cancer biology & therapy · 2013Pooled it
- Hypoxia-mediated epicardial signaling coordinates coronary angiogenesis and myocardial expansion during zebrafish ventricle maturation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cellular mechanometabolism: stimuli and implications.EMBO reports · 2026Review
- Simtuzumab Attenuates Loxl2-Mediated Extracellular Matrix Remodeling and Preserves Cardiac Function inCirculation. Heart failure · 2026Article
- Transient hypoxia followed by progressive reoxygenation is required for muscle repair.EMBO reports · 2026Article
- Verbascoside targets endothelial HIF-1α/ Lysyl oxidase signaling to attenuate glomerular injury in diabetic nephropathy.Redox report : communications in free radical research · 2025Article
- A Prospective Exploratory Study on Potential Systemic Causes and Risk Factors for Subconjunctival Bleeding in Neonatal Calves.Veterinary sciences · 2025Article
- Review
- Systematic Characterisation and Analysis of Lysyl Oxidase Family Members as Drivers of Tumour Progression and Multiple Drug Resistance.Journal of cellular and molecular medicine · 2025Article
- Reactive Oxygen Species and its Manipulation Strategies in Cancer Treatment.Current medicinal chemistry · 2025Review
- Comparative analysis of lipid metabolism in trophoblast subpopulations in preeclampsia andFrontiers in molecular biosciences · 2025Article
- Lysyl Oxidase-like 2 Dysregulation Increases the Risk of Post- Operative Fibrotic Scars Formation in the Female Reproductive Tract: A Novel Therapeutic Target to Reduce Fibrogenesis.Current medicinal chemistry · 2025Review
- LOXL2 inhibition ameliorates pulmonary artery remodeling in pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Distinct phenotypes induced by acute hypoxia and TGF-β1 in human adult cardiac fibroblasts.Journal of molecular and cellular cardiology plus · 2024Article
- Revisiting reactive oxygen species production in hypoxia.Pflugers Archiv : European journal of physiology · 2024Review
- A Comprehensive Review of Protein Biomarkers for Invasive Lung Cancer.Current oncology (Toronto, Ont.) · 2024Review
- Breast Collagen Organization: Variance by Patient Age and Breast Quadrant.Diagnostics (Basel, Switzerland) · 2024Article
- Hypoxia- and Postirradiation reoxygenation-induced HMHA1/ARHGAP45 expression contributes to cancer cell invasion in a HIF-dependent manner.British journal of cancer · 2024Article
- Targeting lysyl oxidase like 2 attenuates OVA-induced airway remodeling partly via the AKT signaling pathway.Respiratory research · 2024Article
83 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Hypoxia has been shown to promote tumor metastasis and lead to therapy resistance. Recent work has demonstrated that hypoxia represses E-cadherin expression, a hallmark of epithelial to mesenchymal transition, which is believed to amplify tumor aggressiveness. The molecular mechanism of E-cadherin repression is unknown, yet lysyl oxidases have been implicated to be involved. Gene expression of lysyl oxidase (LOX) and the related LOX-like 2 (LOXL2) is strongly induced by hypoxia. In addition to the previously demonstrated LOX, we characterize LOXL2 as a direct transcriptional target of HIF-1. We demonstrate that activation of lysyl oxidases is required and sufficient for hypoxic repression of E-cadherin, which mediates cellular transformation and takes effect in cellular invasion assays. Our data support a molecular pathway from hypoxia to cellular transformation. It includes up-regulation of HIF and subsequent transcriptional induction of LOX and LOXL2, which repress E-cadherin and induce epithelial to mesenchymal transition. Lysyl oxidases could be an attractive molecular target for cancers of epithelial origin, in particular because they are partly extracellular.
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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.