Lysyl Oxidase is essential for hypoxia-induced metastasis in breast cancer

Hypoxic tumor cells are highly aggressive and often metastatic, however the underlying processes remain unclear. Lysyl oxidase (LOX) is an enzyme essential for the formation of the extracellular matrix. We show that LOX expression is regulated by HIF-1 and is associated with hypoxia in human breast tumors. Our data demonstrate that patients with high LOX expressing tumors, have poor distant metastasis-free and overall survivals. Inhibition of LOX by shRNA, pharmacological inhibitors or by antibody eliminates metastasis in mice with orthotopically grown breast cancer tumors. Mechanistically, secreted LOX is respo…