LOXL2 explained

Lysyl oxidase homolog 2 is an enzyme that in humans is encoded by the LOXL2 gene.^{[1] [2]}

Function

This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family.

LOXL2 can also crosslink collagen type IV and hence influence the sprouting of new blood vessels.^[3]

Clinical significance

LOXL2 is an enzyme that is up-regulated in several types of cancer and is associated with a poorer prognosis.^{[4] [5]} LOXL2 changes the structure of histones (proteins that are attached to DNA)^[6] and thus changes the shape of the cells, making it easier for the cancer cells to metastasize.^[7]

An antibody that inhibits the activity of LOXL2, simtuzumab, is currently in clinical trials for the treatment of several types of cancer and fibrotic diseases such as liver fibrosis.^[8]

See also

• LOXL1
• LOXL3
• LOXL4

Further reading

• Book: Csiszar K . Lysyl oxidases: a novel multifunctional amine oxidase family . 70 . 1–32 . 2001 . 11642359 . 10.1016/S0079-6603(01)70012-8 . 978-0-12-540070-1 . Progress in Nucleic Acid Research and Molecular Biology .
• Molnar J, Fong KS, He QP, Hayashi K, Kim Y, Fong SF, Fogelgren B, Szauter KM, Mink M, Csiszar K . Structural and functional diversity of lysyl oxidase and the LOX-like proteins . Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics . 1647 . 1–2 . 220–4 . April 2003 . 12686136 . 10.1016/s1570-9639(03)00053-0 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . Jan 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Saito H, Papaconstantinou J, Sato H, Goldstein S . Regulation of a novel gene encoding a lysyl oxidase-related protein in cellular adhesion and senescence . The Journal of Biological Chemistry . 272 . 13 . 8157–60 . March 1997 . 9079631 . 10.1074/jbc.272.13.8157 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Jourdan-Le Saux C, Tronecker H, Bogic L, Bryant-Greenwood GD, Boyd CD, Csiszar K . The LOXL2 gene encodes a new lysyl oxidase-like protein and is expressed at high levels in reproductive tissues . The Journal of Biological Chemistry . 274 . 18 . 12939–44 . April 1999 . 10212285 . 10.1074/jbc.274.18.12939 . free .
• Hein S, Yamamoto SY, Okazaki K, Jourdan-LeSaux C, Csiszar K, Bryant-Greenwood GD . Lysyl oxidases: expression in the fetal membranes and placenta . Placenta . 22 . 1 . 49–57 . Jan 2001 . 11162352 . 10.1053/plac.2000.0580 .
• Akiri G, Sabo E, Dafni H, Vadasz Z, Kartvelishvily Y, Gan N, Kessler O, Cohen T, Resnick M, Neeman M, Neufeld G . Lysyl oxidase-related protein-1 promotes tumor fibrosis and tumor progression in vivo . Cancer Research . 63 . 7 . 1657–66 . April 2003 . 12670920 .
• Rost T, Pyritz V, Rathcke IO, Görögh T, Dünne AA, Werner JA . Reduction of LOX- and LOXL2-mRNA expression in head and neck squamous cell carcinomas . Anticancer Research . 23 . 2B . 1565–73 . 2003 . 12820424 .
• Vadasz Z, Kessler O, Akiri G, Gengrinovitch S, Kagan HM, Baruch Y, Izhak OB, Neufeld G . Abnormal deposition of collagen around hepatocytes in Wilson's disease is associated with hepatocyte specific expression of lysyl oxidase and lysyl oxidase like protein-2 . Journal of Hepatology . 43 . 3 . 499–507 . September 2005 . 16023247 . 10.1016/j.jhep.2005.02.052 .
• Peinado H, Del Carmen Iglesias-de la Cruz M, Olmeda D, Csiszar K, Fong KS, Vega S, Nieto MA, Cano A, Portillo F . A molecular role for lysyl oxidase-like 2 enzyme in snail regulation and tumor progression . The EMBO Journal . 24 . 19 . 3446–58 . October 2005 . 16096638 . 1276164 . 10.1038/sj.emboj.7600781 .
• Akagawa H, Narita A, Yamada H, Tajima A, Krischek B, Kasuya H, Hori T, Kubota M, Saeki N, Hata A, Mizutani T, Inoue I . Systematic screening of lysyl oxidase-like (LOXL) family genes demonstrates that LOXL2 is a susceptibility gene to intracranial aneurysms . Human Genetics . 121 . 3–4 . 377–87 . May 2007 . 17287949 . 10.1007/s00439-007-0333-3 . 25771968 .

Notes and References

1. Jourdan-Le Saux C, Le Saux O, Donlon T, Boyd CD, Csiszar K . The human lysyl oxidase-related gene (LOXL2) maps between markers D8S280 and D8S278 on chromosome 8p21.2-p21.3 . Genomics . 51 . 2 . 305–7 . July 1998 . 9722957 . 10.1006/geno.1998.5356 .
2. Web site: Entrez Gene: LOXL2 lysyl oxidase-like 2.
3. Bignon M, Pichol-Thievend C, Hardouin J, Malbouyres M, Bréchot N, Nasciutti L, Barret A, Teillon J, Guillon E, Etienne E, Caron M, Joubert-Caron R, Monnot C, Ruggiero F, Muller L, Germain S . Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane . Blood . 118 . 14. 3979–89 . 2011 . 21835952 . 10.1182/blood-2010-10-313296 . 16622717 . free .
4. Nishioka T, Eustace A, West C . Lysyl oxidase: from basic science to future cancer treatment . Cell Struct. Funct. . 37 . 1 . 75–80 . 2012 . 22453058 . 10.1247/csf.11015. free .
5. Cano A, Santamaría PG, Moreno-Bueno G . LOXL2 in epithelial cell plasticity and tumor progression . Future Oncol . 8 . 9 . 1095–108 . 2012 . 23030485 . 10.2217/fon.12.105 .
6. Herranz N, Dave N, Millanes-Romero A, Morey L, Díaz VM, Lórenz-Fonfría V, Gutierrez-Gallego R, Jerónimo C, Di Croce L, García de Herreros A, Peiró S . Lysyl oxidase-like 2 deaminates lysine 4 in histone H3 . Molecular Cell . 46 . 3 . 369–376 . 2012 . 22483618 . 10.1016/j.molcel.2012.03.002 . free . 10230/25392 . free .
7. Moreno-Bueno G, Salvador F, Martín A, Floristán A, Cuevas EP, Santos V, Montes A, Morales S, Castilla MA, Rojo-Sebastián A, Martínez A, Hardisson D, Csiszar K, Portillo F, Peinado H, Palacios J, Cano A . Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas . EMBO Mol Med . 3 . 9 . 528–544 . 2011 . 21732535 . 10.1002/emmm.201100156 . 3377095.
8. Web site: Search of: simtuzumab - List Results . ClinicalTrials.gov . 25 February 2015 .