Lysyl oxidase (LOX), known as protein-lysine oxidase 6, is a copper enzyme that catalyzes the conversion of lysine molecules to cross-linked aldehydes in extracellular matrix proteins. Inhibition can cause osteoarthritis its up-regulation by cancer cells promotes the metastasis of the existing tumor.
Lysyl oxidase is an enzyme that catalyzes the formation of aldehydes [from lysine residues] in collagen and elastin precursors resulting in the cross-linking of collagen and elastin, which is necessary for the stabilization of collagen fibers and for collagen and elastin]. The importance of lysyloxidase [animal studies] has been found to be inhibited either by nutritional deficiency of copper or by supplementing a diet with a lysyloxidase inhibitor.
This has led to flaccidity, characterized by poor bone formation and endurance, overexposed skin, weak ligaments and increased aortic aneurysms, abnormalities due to reduced collagen and elastin cross-linking. LOX is critical for cardiovascular development, but plays an important role in connective tissue development, neurological function, respiratory and skin development [collagen and elastin represent 50-60% of lung composition and 75% of skin]. In LOX, double knockout models (Lox – / -) the lung phenotype resembles that of emphysema patients.
LOX expression is regulated by HIFs factors, and therefore LOX expression is upregulated in hypoxic tumors, and patients with high LOX expression tumors have poor overall survival. [LOX inhibition eliminates metastases in mice] .
Secretory LOX is responsible for the penetrating properties of hypoxic cancer cells through focal adhesion kinase activity and cell-to-uterine adhesion, creating a site conducive to recent metastatic development that LOX overexpression is critical to promoting the growth and metastasis of several cancers, including breast, non-small cell lung cancer, and colon cancer. LOX expression was also detected in megakaryocytes, or bone marrow cells responsible for platelet production [myelofibrosis model].
LOX was found to be involved in bone marrow fibrosis. LOX [secreted by hypoxic tumor cells, cross-linking collagen to the basement membrane is necessary for the recruitment of CD11b + [myeloid cells] that attach to cross-linked collagen and produce MMP2 for collagen cleavage, enhancing post-invasive collagen. In contrast, LOX inhibition prevents CD11b + cell recruitment and metastatic growth. In cells that do not have TGF-β receptors, a deficiency that is characteristic of lung cancer, LOX is found in high concentrations and its high expression is associated with a high degree of carcinogenic invasion. patients with early stage adenocarcinoma.
Lysyl oxidase has recently been implicated in tumor angiogenesis, or in the formation of blood vessels [in vivo and in vitro], increasing VEGF expression and secretion, which in turn promotes angiogenesis by phosphorylation of protein kinase B, or Akt, platelet-derived growth factor PDGFRB.
High LOX levels are associated with high blood vessel density. LOX inhibitors are useful in prevention 1] of angiogenesis 2] of tumor evolution 3] of metastasis and treatment of fibrotic diseases a] neurodegenerative b] cardiovascular diseases associated with extracellular matrix remodeling.
NOTE: Resveratrol, curcumin or epigallocatechin, and quercetin suppress LOX.