HBEGF and breast cancer: Studies showed that human breast cancer cells exposed to hypoxia are enough to induce the expression of ADAM12 in a HIF-dependent manner, leading to the shedding of HB-EGF outfield, enhancing EGFR signaling pathway propagation and downstream activation of focal adhesion kinase (FAK) to trigger the breast cancer cells of motility, invasion and metastasis (66).