Fig. 7

Mechanism by which OSM induces LOXL2 and promotes ECM remodeling. OSM binds to gp130, which recruits OSMRβ to form a heterodimer and allow the phosphorylation and activation of downstream signaling pathways, including STAT3, MAPK, and PI3K. OSM signaling promotes EMT in invasive ductal carcinomas and as the data shows LOXL2 expression in its ~ 105 kDa glycosylated form. The 105 kDa LOXL2 is enzymatically active and secreted into the ECM of the breast tumor microenvironment. In the ECM, LOXL2 promotes crosslinking of the main constituent of the stroma, collagen I, which leads to collagen I fiber alignment. The alignment of collagen I fibers in the stroma provides pathways for cancer cells that have undergone EMT to invade nearby tissue and vasculature [52, 53]. Therefore, these changes to the ECM of the tumor microenvironment likely play a functional role in invasive ductal carcinoma metastasis [27, 37]