TY - JOUR
T1 - Endocytic downregulation of ErbB receptors: mechanisms and relevance in cancer.
AU - Roepstorff, Kirstine
AU - Grøvdal, Lene
AU - Grandal, Michael
AU - Lerdrup, Mads
AU - van Deurs, Bo
N1 - Keywords: Animals; Down-Regulation; Endocytosis; Humans; Models, Biological; Neoplasms; Receptor, Epidermal Growth Factor; Signal Transduction; Ubiquitin
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
U2 - 10.1007/s00418-008-0401-3
DO - 10.1007/s00418-008-0401-3
M3 - Journal article
C2 - 18288481
SN - 0948-6143
VL - 129
SP - 563
EP - 578
JO - Histochemistry and Cell Biology
JF - Histochemistry and Cell Biology
IS - 5
ER -
