ArticleCancer research2009
A loss-of-function polymorphism in the propeptide domain of the LOX gene and breast cancer.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Variation in the lysyl oxidase (LOX) gene is associated with keratoconus in family-based and case-control studies.Investigative ophthalmology & visual science · 2012Pooled it
- A loss-of-function polymorphism in the propeptide of lysyl oxidase exacerbates atherosclerosis.JCI insight · 2026Article
- Association of LOX gene G473A polymorphism with the occurrence of allergic rhinitis and efficacy of montelukast sodium in children.Cell cycle (Georgetown, Tex.) · 2023Article
- WDR82-Mediated H3K4me3 Is Associated with Tumor Proliferation and Therapeutic Efficacy in Pediatric High-Grade Gliomas.Cancers · 2023Article
- The Lysyl Oxidase G473A Polymorphism Exacerbates Oral Cancer Development in Humans and Mice.International journal of molecular sciences · 2023Article
- The apoptotic and anti-proliferative effect of Lysyl oxidase propeptide in Y79 human retinoblastoma cells.Molecular vision · 2023Article
- Genetic Factors for Coronary Heart Disease and Their Mechanisms: A Meta-Analysis and Comprehensive Review of Common Variants from Genome-Wide Association Studies.Diagnostics (Basel, Switzerland) · 2022Review
- Functions and Mechanisms of Pro-Lysyl Oxidase Processing in Cancers and Eye Pathologies with a Focus on Diabetic Retinopathy.International journal of molecular sciences · 2022Review
- Expression of LOX Suggests Poor Prognosis in Gastric Cancer.Frontiers in medicine · 2021Article
- Insights into the structure and dynamics of lysyl oxidase propeptide, a flexible protein with numerous partners.Scientific reports · 2018Article
- Inhibition of angiogenesis in endothelial cells by Human Lysyl oxidase propeptide.Scientific reports · 2018Article
- A polymorphism in the lysyl oxidase propeptide domain accelerates carcinogen-induced cancer.Carcinogenesis · 2018Article
- Functional importance of lysyl oxidase family propeptide regions.Journal of cell communication and signaling · 2018Review
- Genetic polymorphisms in key hypoxia-regulated downstream molecules and phenotypic correlation in prostate cancer.BMC urology · 2017Article
- Lysyl oxidase propeptide promotes adipogenesis through inhibition of FGF-2 signaling.Adipocyte · 2017Article
- Lysyl Oxidase Isoforms and Potential Therapeutic Opportunities for Fibrosis and Cancer.Expert opinion on therapeutic targets · 2016Review
- A function-blocking CD47 antibody suppresses stem cell and EGF signaling in triple-negative breast cancer.Oncotarget · 2016Article
- Lysyl oxidase propeptide stimulates osteoblast and osteoclast differentiation and enhances PC3 and DU145 prostate cancer cell effects on bone in vivo.Journal of cell communication and signaling · 2016Article
- Article
- Silencing of hypoxia-inducible tumor suppressor lysyl oxidase gene by promoter methylation activates carbonic anhydrase IX in nasopharyngeal carcinoma.American journal of cancer research · 2014Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The lysyl oxidase (LOX) gene reverted Ras transformation of NIH 3T3 fibroblasts and tumor formation by gastric cancer cells, which frequently carry mutant RAS genes. The secreted lysyl oxidase proenzyme is processed to a propeptide (LOX-PP) and a functional enzyme (LOX). Unexpectedly, the tumor suppressor activity mapped to the LOX-PP domain, which inhibited tumor formation and the invasive phenotype of NF639 breast cancer cells driven by human epidermal growth factor receptor-2/neu, which signals via Ras. A single-nucleotide polymorphism, G473A (rs1800449), resulting in an Arg158Gln substitution in a highly conserved region within LOX-PP, occurs with an average 473A allele carrier frequency of 24.6% in the HapMap database, but was present in many breast cancer cell lines examined. Here, we show that the Arg-to-Gln substitution profoundly impairs the ability of LOX-PP to inhibit the invasive phenotype and tumor formation of NF639 cells in a xenograft model. LOX-PP Gln displayed attenuated ability to oppose the effects of LOX, which promoted a more invasive phenotype. In a case-control study of African American women, a potential association of the Gln-encoding A allele was seen with increased risk of estrogen receptor (ER)-alpha-negative invasive breast cancer in African American women. Consistently, LOX gene expression was higher in ER-negative versus ER-positive primary breast cancers, and LOX-PP Gln was unable to inhibit invasion by ER-negative cell lines. Thus, these findings identify for the first time genetic polymorphism as a mechanism of impaired tumor suppressor function of LOX-PP and suggest that it may play an etiologic role in ER-negative breast cancer.
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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.