Epiregulin-blocking antibody inhibits epiregulin-dependent EGFR signaling

• Published in: Biochemical and biophysical research communications 2017-07, Vol.489 (1), p.83-88
• Main Authors: Iijima, Mariko, Anai, Motonobu, Kodama, Tatsuhiko, Shibasaki, Yoshikazu
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Blocking - immunology; Antibodies, Blocking - pharmacology; Blocking antibody; Cancer; Cell adhesion; Cell Adhesion - drug effects; EGF; EGFR; Epiregulin; Epiregulin - immunology; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Receptor, Epidermal Growth Factor - metabolism; Signal Transduction - drug effects; Structure-Activity Relationship; Tumor Cells, Cultured
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.03.006

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. •Epiregulin (EREG) expression is increased in numerous human cancers.•EREG binds and stimulates epidermal growth factor receptor (EGFR) signaling.•The present anti-EREG antibody (9E5) inhibits EGFR signaling by EREG but not by EGF.•The 9E5 antibody may serve as therapeutic candidates for the treatment of cancers.