TY - JOUR
T1 - Nuclear functions and subcellular trafficking mechanisms of the epidermal growth factor receptor family
AU - Wang, Ying Nai
AU - Hung, Mien Chie
N1 - Funding Information:
This review is based on my Presidential Award Lecture at the 2011 SCBA biannual meeting in Guangzhou, China. We thank Dr. Jung-Mao Hsu for the diagram of the proposed model. We also thank Dr. Walter J. Pagel at Department of Scientific Publications and Dr. Jennifer L. Hsu for editing this manuscript. This current study was supported by the National Institutes of Health Grants NIH RO1 CA 109311; NIH PO1 CA 099031; the National Breast Cancer Foundation, Inc.; and the Sister Institutional Fund from China Medical University Hospital and MD Anderson Cancer Center. This work was also supported by the Cancer Research Center of Excellence Grant DOH101-TD-C-111-005; and NSC99-2632-B-039-001-MY3 from Taiwan.
PY - 2012/4/20
Y1 - 2012/4/20
N2 - Accumulating evidence suggests that various diseases, including many types of cancer, result from alteration of subcellular protein localization and compartmentalization. Therefore, it is worthwhile to expand our knowledge in subcellular trafficking of proteins, such as epidermal growth factor receptor (EGFR) and ErbB-2 of the receptor tyrosine kinases, which are highly expressed and activated in human malignancies and frequently correlated with poor prognosis. The well-characterized trafficking of cell surface EGFR is routed, via endocytosis and endosomal sorting, to either the lysosomes for degradation or back to the plasma membrane for recycling. A novel nuclear mode of EGFR signaling pathway has been gradually deciphered in which EGFR is shuttled from the cell surface to the nucleus after endocytosis, and there, it acts as a transcriptional regulator, transmits signals, and is involved in multiple biological functions, including cell proliferation, tumor progression, DNA repair and replication, and chemo- and radio-resistance. Internalized EGFR can also be transported from the cell surface to several intracellular compartments, such as the Golgi apparatus, the endoplasmic reticulum, and the mitochondria, in addition to the nucleus. In this review, we will summarize the functions of nuclear EGFR family and the potential pathways by which EGFR is trafficked from the cell surface to a variety of cellular organelles. A better understanding of the molecular mechanism of EGFR trafficking will shed light on both the receptor biology and potential therapeutic targets of anti-EGFR therapies for clinical application.
AB - Accumulating evidence suggests that various diseases, including many types of cancer, result from alteration of subcellular protein localization and compartmentalization. Therefore, it is worthwhile to expand our knowledge in subcellular trafficking of proteins, such as epidermal growth factor receptor (EGFR) and ErbB-2 of the receptor tyrosine kinases, which are highly expressed and activated in human malignancies and frequently correlated with poor prognosis. The well-characterized trafficking of cell surface EGFR is routed, via endocytosis and endosomal sorting, to either the lysosomes for degradation or back to the plasma membrane for recycling. A novel nuclear mode of EGFR signaling pathway has been gradually deciphered in which EGFR is shuttled from the cell surface to the nucleus after endocytosis, and there, it acts as a transcriptional regulator, transmits signals, and is involved in multiple biological functions, including cell proliferation, tumor progression, DNA repair and replication, and chemo- and radio-resistance. Internalized EGFR can also be transported from the cell surface to several intracellular compartments, such as the Golgi apparatus, the endoplasmic reticulum, and the mitochondria, in addition to the nucleus. In this review, we will summarize the functions of nuclear EGFR family and the potential pathways by which EGFR is trafficked from the cell surface to a variety of cellular organelles. A better understanding of the molecular mechanism of EGFR trafficking will shed light on both the receptor biology and potential therapeutic targets of anti-EGFR therapies for clinical application.
KW - EGFR family receptors
KW - Nuclear translocation
KW - Subcellular trafficking
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U2 - 10.1186/2045-3701-2-13
DO - 10.1186/2045-3701-2-13
M3 - Review article
C2 - 22520625
AN - SCOPUS:84864589406
SN - 2045-3701
VL - 2
JO - Cell and Bioscience
JF - Cell and Bioscience
IS - 1
M1 - 13
ER -