ArticleMolecular and cellular biology2011
The Ras signaling inhibitor LOX-PP interacts with Hsp70 and c-Raf to reduce Erk activation and transformed phenotype of breast cancer cells.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- Lysyl Oxidases as Targets for Cancer Therapy and Diagnostic Imaging.ChemMedChem · 2023Review
- Mechanistic insight into lysyl oxidase in vascular remodeling and angiogenesis.Genes & diseases · 2023Review
- The apoptotic and anti-proliferative effect of Lysyl oxidase propeptide in Y79 human retinoblastoma cells.Molecular vision · 2023Article
- LOX upregulates FAK phosphorylation to promote metastasis in osteosarcoma.Genes & diseases · 2023Article
- 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
- Serum Lysyl Oxidase Levels and Lysyl Oxidase Gene Polymorphism in Ovarian Cancer Patients of Eastern Indian Population.Diagnostics (Basel, Switzerland) · 2021Article
- Lysyl oxidases: linking structures and immunity in the tumor microenvironment.Cancer immunology, immunotherapy : CII · 2020Review
- Effects of High Glucose-Induced Lysyl Oxidase Propeptide on Retinal Endothelial Cell Survival: Implications for Diabetic Retinopathy.The American journal of pathology · 2019Article
- Divergent roles of lysyl oxidase family members in ornithine decarboxylase- and RAS-transformed mouse fibroblasts and human melanoma cells.Oncotarget · 2018Article
- 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
- Functional importance of lysyl oxidase family propeptide regions.Journal of cell communication and signaling · 2018Review
- Nuclear expression of lysyl oxidase enzyme is an independent prognostic factor in rectal cancer patients.Oncotarget · 2017Article
- Lysyl Oxidase Isoforms and Potential Therapeutic Opportunities for Fibrosis and Cancer.Expert opinion on therapeutic targets · 2016Review
- 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
- Determination of cell uptake pathways for tumor inhibitor lysyl oxidase propeptide.Molecular oncology · 2016Article
- Article
- EWS/FLI1 Target Genes and Therapeutic Opportunities in Ewing Sarcoma.Frontiers in oncology · 2015Review
- Human copper-dependent amine oxidases.Archives of biochemistry and biophysics · 2014Review
- Genome-wide expression analysis of HSP70 family genes in rice and identification of a cytosolic HSP70 gene highly induced under heat stress.Functional & integrative genomics · 2013Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The lysyl oxidase gene (LOX) inhibits Ras signaling in transformed fibroblasts and breast cancer cells. Its activity was mapped to the 162-amino-acid propeptide domain (LOX-PP) of the lysyl oxidase precursor protein. LOX-PP inhibits Erk signaling, motility, and tumor formation in a breast cancer xenograft model; however, its mechanism of action is largely unknown. Here, a copurification-mass spectrometry approach was taken using ectopically expressed LOX-PP in HEK293T cells and the heat shock/chaperone protein Hsp70 identified. Hsp70 interaction with LOX-PP was confirmed using coimmunoprecipitation of intracellularly and bacterially expressed and endogenous proteins. The interaction was mapped to the Hsp70 peptide-binding domain and to LOX-PP amino acids 26 to 100. LOX-PP association reduced Hsp70 chaperone activities of protein refolding and survival after heat shock. LOX-PP interacted with the Hsp70 chaperoned protein c-Raf. With the use of ectopic expression of LOX-PP wild-type and deletion proteins, small interfering RNA (siRNA) knockdown, and Lox(-/-) mouse embryo fibroblasts, LOX-PP interaction with c-Raf was shown to decrease downstream activation of MEK and NF-κB, migration, and anchorage-independent growth and reduce its mitochondrial localization. Thus, the interaction of LOX-PP with Hsp70 and c-Raf inhibits a critical intermediate in Ras-induced MEK signaling and plays an important role in the function of this tumor suppressor.
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