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

Heparin-binding EGF-like growth factor (HBEGF), also widely known as the human diphtheria toxin receptor, is a member of the epidermal growth factor (EGF) family synthesized as a membrane-anchored precursor. It functions as a potent mitogen and chemotactic factor for various cell types and is critical for physiological processes such as wound healing, cardiac development, and blastocyst implantation [1][2]. HB-EGF exerts its biological effects by binding to and activating the EGF receptor (EGFR/ErbB1) and ErbB4 [3]. Crucially, it serves as the high-affinity cell surface receptor for the diphtheria toxin produced by Corynebacterium diphtheriae, facilitating the toxin's entry into the cell through receptor-mediated endocytosis [4]. In pathology, HBEGF is frequently overexpressed in numerous malignancies, including ovarian, breast, and gastric cancers, where it promotes tumor progression and chemotherapy resistance [5]. Consequently, it is a target for therapeutic intervention using inhibitors like CRM197, a non-toxic mutant of the diphtheria toxin that specifically blocks HB-EGF signaling [6]. Sources: [1] UniProt (Q99075) [2] PubMed (PMID: 15546814) [3] PubMed (PMID: 10446141) [4] PubMed (PMID: 1530616) [5] PubMed (PMID: 21903022) [6] PubMed (PMID: 12433695)

Other names

Diphtheria toxin receptorDTRHB-EGFDTSHEGFLHeparin-binding epidermal growth factor-like growth factor

Binding to the receptor facilitates receptor-mediated endocytosis of toxins (e.g., Diphtheria toxin) leading to protein synthesis inhibition; inhibition of the growth factor by antagonists (e.g., CRM197) prevents activation of EGFR/ErbB4 signaling pathways in cancer cells.