Disease relevance of LOXL2

• 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 [1].
• Loxl2 also catalyzed the oxidation of cell surface proteins on HepG2 hepatoblastoma cells and inhibited their proliferation [1].
• The upregulation of Lox and Loxl2 in Wilson's disease could perhaps be utilized for diagnostic purposes since their expression is up-regulated in hepatocytes even before the onset of fibrosis [1].
• LOX and LOXL2 showed the strongest association with invasive potential in both highly invasive/metastatic breast cancer cell lines tested (MDA-MB-231 and Hs578T) [2].
• The cancer-related functions of both LOX and LOXL2 have not yet been investigated in squamous cell carcinoma of the head and neck (HNSCC) [3].

High impact information on LOXL2

• Overexpression of LOXL2 or LOXL3 in epithelial cells induces an EMT process, supporting their implication in tumor progression [4].
• The biological importance of LOXL2 is further supported by RNA interference of LOXL2 in Snail-expressing metastatic carcinoma cells, which led to a strong decrease of tumor growth associated to increased apoptosis and reduced expression of mesenchymal and invasive/angiogenic markers [4].
• The LOXL2 gene encodes a new lysyl oxidase-like protein and is expressed at high levels in reproductive tissues [5].
• In situ hybridization identified placental syncytial and cytotrophoblasts responsible for the synthesis of LOXL2 mRNA and demonstrated a spatial and temporal expression pattern unique to the LOXL2 gene [5].
• Expression of the LOXL2 gene was detected in almost all tissues with the highest steady state mRNA levels in the reproductive tissues, placenta, uterus and prostate [5].

Biological context of LOXL2

• Sequences corresponding to the 3' untranslated regions of LOX, LOXL1, and LOXL2 were individually queried against the human expressed sequence tag database (dbEST) [6].
• However, specific novel functions, such as a potential role in cell adhesion and cell growth control, will be determined by other, conserved domains such as the cytokine receptor-like domain that is shared by all LOXs and by multiple scavenger receptor cysteine-rich (SRCR) domains present in LOXL2 and LOXL3 [7].
• Exon 1 of the LOXL2 gene does not encode a signal sequence that is present in LOX and LOXL, suggesting a different processing and intracellular localization for this new protein [5].
• The human lysyl oxidase-related gene (LOXL2) maps between markers D8S280 and D8S278 on chromosome 8p21.2-p21.3 [8].
• This full-length cDNA clone of 3432 base pairs (WS9-14) was isolated from human fibroblasts on the basis of its overexpression in senescent cells [9].

Anatomical context of LOXL2

• LOXL2 expression was again different and was expressed predominantly in the chorionic cytotrophoblast of the membranes with low expression in both the amnion and placentae [10].
• MATERIALS AND METHODS: We examined the mRNA levels of LOX and LOXL2 in ten malignantly transformed cell lines and sixteen malignant tissue samples of different graded and staged HNSCC by RT-PCR [3].
• The pattern of WS9-14 gene expression by fibroblasts parallels pro-collagen I-alpha1 expression [9].

Associations of LOXL2 with chemical compounds

• We have found that Loxl2 is able to oxidize lysine residues of collagen, and behaves in that respect similarly to Lox [1].
• The copper chelator D-penicillamine inhibits Loxl2 induced oxidation of collagen but the Lox inhibitor beta-aminopropionitrile did not inhibit the oxidation using a BAPN concentration at which Lox activity was completely inhibited [1].

References