ABSTRACT
Lysyl oxidase like 3 (LOXL3) is a copper-dependent amine oxidase responsible for the crosslinking of collagen and elastin in the extracellular matrix. LOXL3 belongs to a family including other members: LOX, LOXL1, LOXL2, and LOXL4. Autosomal recessive mutations are rare and described in patients with Stickler syndrome, early-onset myopia and non-syndromic cleft palate. Along with an essential function in embryonic development, multiple biological functions have been attributed to LOXL3 in various pathologies related to amino oxidase activity. Additionally, various novel roles have been described for LOXL3, such as the oxidation of fibronectin in myotendinous junction formation, and of deacetylation and deacetylimination activities of STAT3 to control of inflammatory response. In tumors, three distinct roles were described: (1) LOXL3 interacts with SNAIL and contributes to proliferation and metastasis by inducing epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma cells; (2) LOXL3 is localized predominantly in the nucleus associated with invasion and poor gastric cancer prognosis; (3) LOXL3 interacts with proteins involved in DNA stability and mitosis completion, contributing to melanoma progression and sustained proliferation. Here we review the structure, function and activity of LOXL3 in normal and pathological conditions and discuss the potential of LOXL3 as a therapeutic target in various diseases.
Subject(s)
Amino Acid Oxidoreductases/genetics , Arthritis/genetics , Cleft Palate/genetics , Connective Tissue Diseases/genetics , Extracellular Matrix/genetics , Hearing Loss, Sensorineural/genetics , Myopia/genetics , Neoplasms/genetics , Retinal Detachment/genetics , Amino Acid Oxidoreductases/chemistry , Amino Acid Oxidoreductases/metabolism , Arthritis/enzymology , Arthritis/pathology , Cleft Palate/enzymology , Cleft Palate/pathology , Collagen/chemistry , Collagen/genetics , Collagen/metabolism , Connective Tissue Diseases/enzymology , Connective Tissue Diseases/pathology , Elastin/chemistry , Elastin/genetics , Elastin/metabolism , Epithelial-Mesenchymal Transition/genetics , Extracellular Matrix/chemistry , Extracellular Matrix/enzymology , Gene Expression Regulation , Hearing Loss, Sensorineural/enzymology , Hearing Loss, Sensorineural/pathology , Humans , Isoenzymes/chemistry , Isoenzymes/genetics , Isoenzymes/metabolism , Myopia/enzymology , Myopia/pathology , Neoplasms/enzymology , Neoplasms/pathology , Organ Specificity , Retinal Detachment/enzymology , Retinal Detachment/pathology , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Signal Transduction , Snail Family Transcription Factors/genetics , Snail Family Transcription Factors/metabolismABSTRACT
Sensorineural hearing loss occurs in approximately 75% of symptomatic children with profound biotinidase deficiency, which is more common than originally thought. The hearing loss varies in severity and is usually irreversible. The biochemical, genotype, and clinical variations do not correlate with the development of hearing loss. Thus, it is very important to diagnose the disorder early, especially by newborn screening, to prevent the hearing loss.