Heparin-binding EGF-like growth factor (HB-EGF) (HB-EGF)

Heparin-binding EGF-like growth factor (HB-EGF) is a member of the epidermal growth factor (EGF) family, synthesized as a membrane-anchored precursor known as pro-HB-EGF (UniProt Q99075). It undergoes proteolytic cleavage, a process called ectodomain shedding, to release a soluble form (sHB-EGF) that acts as a potent agonist for the EGFR (ErbB1) and ErbB4 receptors (Miyamoto et al., 2006). Uniquely, the membrane-anchored precursor also serves as the cellular receptor for diphtheria toxin, making it a target for toxin-based therapies (Naglich et al., 1992). HB-EGF is frequently overexpressed in various malignancies, including ovarian, breast, and gastric cancers, where it drives tumor progression, chemoresistance, and angiogenesis (Yagi et al., 2003). Therapeutic strategies targeting HB-EGF include neutralizing monoclonal antibodies and diphtheria toxin derivatives like CRM197, which aim to block its mitogenic signaling or induce targeted cell death (Miyamoto et al., 2006). However, because HB-EGF plays critical roles in cardiac homeostasis and skin wound healing, targeting it carries risks of cardiotoxicity and impaired tissue repair (Iwamoto et al., 2003).

Other names

HBEGFDiphtheria toxin receptorDTRProheparin-binding EGF-like growth factorDTSHEGFL

Neutralization of the soluble ligand to prevent activation of EGFR and ErbB4 receptors, and inhibition of the proteolytic shedding of the membrane-anchored precursor (Miyamoto et al., 2006).