TY - JOUR
T1 - Nuclear EGFR signalling network in cancers
T2 - Linking EGFR pathway to cell cycle progression, nitric oxide pathway and patient survival
AU - Lo, H. W.
AU - Hung, M. C.
N1 - Funding Information:
This study is partially supported by RO-1 CA109311, PO-1 CA99031, the P50 83639, P20 CA101936 and MD Anderson Cancer Center, Cancer Center Supporting Grant, CA16672 (to M-CH) from the National Institute of Health. H-WL is a recipient of the Post-doctoral Fellowships from the American Cancer Society (PF-05-175-01-TBE to H-WL).
PY - 2006/1/30
Y1 - 2006/1/30
N2 - Emerging evidences suggest the existence of a new mode of epidermal growth factor receptor (EGFR) signalling pathway in which activated EGFR undergoes nuclear translocalization and subsequently regulates gene expression and potentially mediates other cellular processes. This signalling route is distinct from the better-characterized, traditional EGFR pathway that involves transduction of mitogenic signals through activation of multiple signalling cascades. Transcriptional activity of nuclear EGFR appears to depend on its C-terminal transactivation domain and its physical and functional interaction with other transcription factors that contain DNA-binding activity. Likely via its ability to upregulate gene expression, nuclear EGFR pathway is associated with major characteristics of more aggressive tumours: increased proliferative potential, nitric oxide synthesis, and accelerated GI/S cell cycle progression. A role of nuclear EGFR in prognostic prediction is further suggested in patients with breast carcinomas and oropharyngeal squamous cell carcinomas. It is noted that significant advances were made towards the knowledge of the nuclear EGFR pathway; however, many aspects of this new pathway remain unresolved and will be discussed in this review. As a number of other receptor tyrosine kinases (RTKs) and cytokine receptors also undergo similar nuclear translocalization, a better understanding of the physiological and malignant nature of the nuclear EGFR pathway will likely shed light into the biology of cancer with nuclear RTKs.
AB - Emerging evidences suggest the existence of a new mode of epidermal growth factor receptor (EGFR) signalling pathway in which activated EGFR undergoes nuclear translocalization and subsequently regulates gene expression and potentially mediates other cellular processes. This signalling route is distinct from the better-characterized, traditional EGFR pathway that involves transduction of mitogenic signals through activation of multiple signalling cascades. Transcriptional activity of nuclear EGFR appears to depend on its C-terminal transactivation domain and its physical and functional interaction with other transcription factors that contain DNA-binding activity. Likely via its ability to upregulate gene expression, nuclear EGFR pathway is associated with major characteristics of more aggressive tumours: increased proliferative potential, nitric oxide synthesis, and accelerated GI/S cell cycle progression. A role of nuclear EGFR in prognostic prediction is further suggested in patients with breast carcinomas and oropharyngeal squamous cell carcinomas. It is noted that significant advances were made towards the knowledge of the nuclear EGFR pathway; however, many aspects of this new pathway remain unresolved and will be discussed in this review. As a number of other receptor tyrosine kinases (RTKs) and cytokine receptors also undergo similar nuclear translocalization, a better understanding of the physiological and malignant nature of the nuclear EGFR pathway will likely shed light into the biology of cancer with nuclear RTKs.
KW - Cell cycle control
KW - Epidermal growth factor receptor
KW - Inducible nitric oxide synthase
KW - Receptor tyrosine kinase
KW - Transcriptional regulation
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U2 - 10.1038/sj.bjc.6602941
DO - 10.1038/sj.bjc.6602941
M3 - Short survey
C2 - 16434982
AN - SCOPUS:31444440292
SN - 0007-0920
VL - 94
SP - 184
EP - 188
JO - British journal of cancer
JF - British journal of cancer
IS - 2
ER -