Paradoxical roles for lysyl oxidases in cancer--a prospect.
Lysyl oxidase (LOX) is an extracellular matrix (ECM) enzyme that catalyzes the cross-linking of collagens or elastin in the extracellular compartment, thereby regulating the tensile strength of tissues. However, recent reports have demonstrated novel roles for LOX, including the ability to regulate gene transcription, motility/migration, and cell adhesion. These diverse functions have led researchers to hypothesize that LOX may have multiple roles affecting both extra- and intracellular cell function(s). Particularly noteworthy is aberrant LOX expression and activity that have been observed in various cancerous tissues and neoplastic cell lines. Both down and upregulation of LOX in tumor tissues and cancer cell lines have been described, suggesting a dual role for LOX as a tumor suppressor, as well as a metastasis promoter gene--creating a conundrum within the LOX research field. Here, we review the body of evidence on LOX gene expression, regulation, and function(s) in various cancer cell types and tissues, as well as stromal-tumor cell interactions. Lastly, we will examine putative mechanisms in which LOX facilitates breast cancer invasion and metastasis. Taken together, the literature demonstrates the increasingly important role(s) that LOX may play in regulating tumor progression and the necessity to elucidate its myriad mechanisms of action in order to identify potentially novel therapeutics.
Payne
Stacey L
SL
Children's Memorial Research Center, Division of Cancer Biology and Epigenomics, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine at Northwestern University, Chicago, IL 60614, USA.
Hendrix
Mary J C
MJ
Kirschmann
Dawn A
DA
D003300:Copper / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D004848:Epithelium / Q000502:physiology; D005109:Extracellular Matrix / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D016147:Genes, Tumor Suppressor; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D013379:Substrate Specificity
D003300:Copper; D008249:Protein-Lysine 6-Oxidase