Review

Histochemistry and Cell Biology

, Volume 129, Issue 5, pp 563-578

Open Access This content is freely available online to anyone, anywhere at any time.

Endocytic downregulation of ErbB receptors: mechanisms and relevance in cancer

  • Kirstine RoepstorffAffiliated withDepartment of Cellular and Molecular Medicine, the Panum Institute, University of Copenhagen
  • , Lene GrøvdalAffiliated withDepartment of Cellular and Molecular Medicine, the Panum Institute, University of Copenhagen
  • , Michael GrandalAffiliated withDepartment of Cellular and Molecular Medicine, the Panum Institute, University of Copenhagen
  • , Mads LerdrupAffiliated withDepartment of Cellular and Molecular Medicine, the Panum Institute, University of Copenhagen
  • , Bo van DeursAffiliated withDepartment of Cellular and Molecular Medicine, the Panum Institute, University of Copenhagen Email author 

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.

Keywords

Epidermal growth factor receptor Endocytosis Lysosomal degradation ErbB2 Ubiquitin Endosomal sorting