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PMID: 18288481 Published · ppublish English Journal Article Review

Endocytic downregulation of ErbB receptors: mechanisms and relevance in cancer.

Histochemistry and cell biology ·Vol. 129 ·No. 5 ·2008-05-00 ·Pages 563-78

Roepstorff K, Grøvdal L, Grandal M, Lerdrup M, van Deurs B

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.

MeSH Terms
Animals Down-Regulation Endocytosis/physiology ErbB Receptors/metabolism Humans Models, Biological Neoplasms/metabolism,pathology Signal Transduction Ubiquitin/metabolism
Chemicals
Ubiquitin ErbB Receptors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Roepstorff Kirstine
Department of Cellular and Molecular Medicine, the Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark. kirroep@sund.ku.dk
Grøvdal Lene
Grandal Michael
Lerdrup Mads
van Deurs Bo
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Article Info
Journal
Histochemistry and cell biology
Abbr.
Histochem Cell Biol
ISSN
0948-6143
DOI
10.1007/s00418-008-0401-3
Email
kirroep@sund.ku.dk
Published
2008-05-00
Epub
2008-00-21
Pages
563-78
Language
English
Region
Germany
NLM ID
9506663
PMCID
PMC2323030
Subset
IM
External Links
PubMed source DOI: 10.1007/s00418-008-0401-3 PMC Full Text View journal details
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