title: Endocytic downregulation of ErbB receptors: mechanisms and relevance in cancer.
abstract: ErbB receptors (EGFR (ErbB1), ErbB2, ErbB3, and ErbB4) are important regulators of normal growth and differentiation, and they are involved in the pathogenesis of cancer. Following ligand binding and receptor activation, EGFR is endocytosed and transported to lysosomes where the receptor is degraded. This downregulation of EGFR is a complex and tightly regulated process. The functions of ErbB2, ErbB3, and ErbB4 are also regulated by endocytosis to some extent, although the current knowledge of these processes is sparse. Impaired endocytic downregulation of signaling receptors is frequently associated with cancer, since it can lead to increased and uncontrolled receptor signaling. In this review we describe the current knowledge of ErbB receptor endocytic downregulation. In addition, we outline how ErbB receptors can escape endocytic downregulation in cancer, and we discuss how targeted anti-cancer therapy may induce endocytic downregulation of ErbB receptors.
authors.affiliation: Department of Cellular and Molecular Medicine, the Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark. kirroep@sund.ku.dk
authors.forename: Kirstine
authors.initials: K
authors.lastname: Roepstorff
authors.forename: Lene
authors.initials: L
authors.lastname: Grøvdal
authors.forename: Michael
authors.initials: M
authors.lastname: Grandal
authors.forename: Mads
authors.initials: M
authors.lastname: Lerdrup
authors.forename: Bo
authors.initials: B
authors.lastname: van Deurs
mesh_terms: D000818:Animals; D015536:Down-Regulation; D004705:Endocytosis / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D025801:Ubiquitin; D066246:ErbB Receptors