title: Epiregulin-blocking antibody inhibits epiregulin-dependent EGFR signaling.
abstract: The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase involved in many cellular functions including cell growth and migration. EGFR may be activated by EGF family ligands such as EGF and epiregulin (EREG). EREG is overexpressed in human colon and breast cancers, implying that EREG plays roles in tumorigenesis. Although EGF family members share a receptor, it is not well known whether their signaling pathways differ. In order to investigate EREG signaling, we established the anti-EREG antibody that inhibits EGFR downstream signaling stimulated by EREG but not by EGF. While the anti-EREG antibody has little effect on cell growth, it inhibits cell adhesion of EREG-expressing autocrine cancer cell lines. Our results suggest that anti-EREG antibodies represent valuable tools for elucidating EREG-specific signaling pathways, and may serve as therapeutic candidates for the treatment of cancers.
authors.affiliation: Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Iijima
authors.affiliation: Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan.
authors.forename: Motonobu
authors.initials: M
authors.lastname: Anai
authors.affiliation: Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.affiliation: Laboratory for Systems Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904, Japan. Electronic address: shibasaki@lsbm.org.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Shibasaki
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology* / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D066260:Epiregulin / Q000276:immunology*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D019138:Antibodies, Blocking; C587880:EREG protein, human; D066260:Epiregulin; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Blocking antibody; Cancer; Cell adhesion; EGF; EGFR; Epiregulin