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    Epiregulin-blocking antibody inhibits epiregulin-dependent EGFR signaling.
    Biochem Biophys Res Commun 2017 Jul 6;489(1):83-88. Epub 2017 Mar 6.
    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:
    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.

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    High epiregulin expression in human U87 glioma cells relies on IRE1α and promotes autocrine growth through EGF receptor.
    BMC Cancer 2013 Dec 13;13:597. Epub 2013 Dec 13.
    Inserm, LAMC, UMR 1029, Talence F-33400, France.
    Background: Epidermal growth factor (EGF) receptors contribute to the development of malignant glioma. Here we considered the possible implication of the EGFR ligand epiregulin (EREG) in glioma development in relation to the activity of the unfolded protein response (UPR) sensor IRE1α. We also examined EREG status in several glioblastoma cell lines and in malignant glioma. Read More
    Epiregulin contributes to breast tumorigenesis through regulating matrix metalloproteinase 1 and promoting cell survival.
    Mol Cancer 2015 Jul 29;14:138. Epub 2015 Jul 29.
    Department of Lab Medicine and Pathology, University of Minnesota, 2231 6th St SE, Minneapolis, MN, 55455, USA.
    Background: The epidermal growth factor (EGF) family of ligands has been implicated in promoting breast cancer initiation, growth and progression. The contributions of EGF family ligands and their receptors to breast cancer are complex, and the specific mechanisms through which different ligands regulate breast tumor initiation and growth are not well-defined. These studies focus on the EGF family member epiregulin (EREG) as a mediator of early stage breast tumorigenesis. Read More
    Integrin α6β4 Promotes Autocrine Epidermal Growth Factor Receptor (EGFR) Signaling to Stimulate Migration and Invasion toward Hepatocyte Growth Factor (HGF).
    J Biol Chem 2015 Nov 17;290(45):27228-38. Epub 2015 Sep 17.
    From the Markey Cancer Center, Departments of Molecular and Cellular Biochemistry,
    Integrin α6β4 is up-regulated in pancreatic adenocarcinomas where it contributes to carcinoma cell invasion by altering the transcriptome. In this study, we found that integrin α6β4 up-regulates several genes in the epidermal growth factor receptor (EGFR) pathway, including amphiregulin (AREG), epiregulin (EREG), and ectodomain cleavage protease MMP1, which is mediated by promoter demethylation and NFAT5. The correlation of these genes with integrin α6β4 was confirmed in The Cancer Genome Atlas Pancreatic Cancer Database. Read More
    Mammary tumorigenesis induced by fibroblast growth factor receptor 1 requires activation of the epidermal growth factor receptor.
    J Cell Sci 2011 Sep 24;124(Pt 18):3106-17. Epub 2011 Aug 24.
    Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
    Fibroblast growth factor receptor 1 (FGFR1) is an oncoprotein with known involvement in mammary tumorigenesis. To understand how FGFR1 signaling promotes mammary tumorigenesis, an inducible FGFR1 (iFGFR1) system was created previously. Previous studies have demonstrated that upon iFGFR1 activation in vivo, the epidermal growth factor (EGF) ligands amphiregulin (AREG) and epiregulin (EREG) are upregulated. Read More