This gene encodes a member of thelysyl oxidase gene family. The prototypic member of the family is essential to thebiogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks incollagens andelastin. A highly conserved amino acid sequence at theC-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. TheN-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, andchemotaxis to each member of the family.[6]
LOXL2 can also crosslinkcollagen type IV and hence influence the sprouting of newblood vessels.[7]
LOXL2 is an enzyme that is up-regulated in several types of cancer and is associated with a poorer prognosis.[8][9] LOXL2 changes the structure ofhistones (proteins that are attached to DNA)[10] and thus changes the shape of the cells, making it easier for the cancer cells tometastasize.[11]
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 asliver fibrosis.[12]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Jourdan-Le Saux C, Le Saux O, Donlon T, Boyd CD, Csiszar K (July 1998). "The human lysyl oxidase-related gene (LOXL2) maps between markers D8S280 and D8S278 on chromosome 8p21.2-p21.3".Genomics.51 (2):305–7.doi:10.1006/geno.1998.5356.PMID9722957.
^Cano A, Santamaría PG, Moreno-Bueno G (2012). "LOXL2 in epithelial cell plasticity and tumor progression".Future Oncol.8 (9):1095–108.doi:10.2217/fon.12.105.PMID23030485.
^Cebrià-Costa, J. P.; Pascual-Reguant, L.; Gonzalez-Perez, A.; Serra-Bardenys, G.; Querol, J.; Cosín, M.; Verde, G.; Cigliano, R. A.; Sanseverino, W.; Segura-Bayona, S.; Iturbide, A.; Andreu, D.; Nuciforo, P.; Bernado-Morales, C.; Rodilla, V.; Arribas, J.; Yelamos, J.; de Herreros, A. Garcia; Stracker, T. H.; Peiró, S. (2 January 2020). "LOXL2-mediated H3K4 oxidation reduces chromatin accessibility in triple-negative breast cancer cells".Oncogene.39 (1):79–121.doi:10.1038/s41388-019-0969-1.hdl:10230/44004.
Molnar J, Fong KS, He QP, Hayashi K, Kim Y, Fong SF, Fogelgren B, Szauter KM, Mink M, Csiszar K (April 2003). "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.doi:10.1016/s1570-9639(03)00053-0.PMID12686136.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides".Gene.138 (1–2):171–4.doi:10.1016/0378-1119(94)90802-8.PMID8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library".Gene.200 (1–2):149–56.doi:10.1016/S0378-1119(97)00411-3.PMID9373149.
Hein S, Yamamoto SY, Okazaki K, Jourdan-LeSaux C, Csiszar K, Bryant-Greenwood GD (January 2001). "Lysyl oxidases: expression in the fetal membranes and placenta".Placenta.22 (1):49–57.doi:10.1053/plac.2000.0580.PMID11162352.
Akiri G, Sabo E, Dafni H, Vadasz Z, Kartvelishvily Y, Gan N, Kessler O, Cohen T, Resnick M, Neeman M, Neufeld G (April 2003). "Lysyl oxidase-related protein-1 promotes tumor fibrosis and tumor progression in vivo".Cancer Research.63 (7):1657–66.PMID12670920.
Rost T, Pyritz V, Rathcke IO, Görögh T, Dünne AA, Werner JA (2003). "Reduction of LOX- and LOXL2-mRNA expression in head and neck squamous cell carcinomas".Anticancer Research.23 (2B):1565–73.PMID12820424.
Vadasz Z, Kessler O, Akiri G, Gengrinovitch S, Kagan HM, Baruch Y, Izhak OB, Neufeld G (September 2005). "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.doi:10.1016/j.jhep.2005.02.052.PMID16023247.
Akagawa H, Narita A, Yamada H, Tajima A, Krischek B, Kasuya H, Hori T, Kubota M, Saeki N, Hata A, Mizutani T, Inoue I (May 2007). "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.doi:10.1007/s00439-007-0333-3.PMID17287949.S2CID25771968.
