EGF and cancer: EGFR signaling in invadopodia might be also sustained by a high level of heparin-binding (HB)-EGF, which is synthesized as pro-HB-EGF and subsequently cleaved by ADAM-12 to release a soluble form binding to EGFR, providing an advantage for cancer cells to intravasate, invade and metastasize (Zhou et al., 2014).