These responses require the up-regulation of lysyl oxidase enzymes (LOX, LOXL2, and LOXL4), which are produced by hypoxic BC cells released in the bloodstream and accumulated at premetastatic niche, where they enable the remodeling of collagen and other ECM molecules toward the intravasation of circulating BC cells (Schito and Semenza, 2016). This evidence concerns the gene LOX and breast cancer.