Open AccessJournal Article
The nuclear epidermal growth factor receptor signaling network and its role in cancer
TLDR
The current knowledge of the nuclear EGFR signaling network is summarized, including how it is trafficked to the nucleus, the functions it serves inThe nucleus, and how these functions impact cancer progression, survival, and response to chemotherapeutics.Abstract:
The epidermal growth factor receptor (EGFR) is a member of the EGFR family of receptor tyrosine kinases (RTKs). EGFR activation via ligand binding results in signaling through various pathways ultimately resulting in cellular proliferation, survival, angiogenesis, invasion, and metastasis. Aberrant expression or activity of EGFR has been strongly linked to the etiology of several human epithelial cancers including but not limited to head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), colorectal cancer (CRC), breast cancer, pancreatic cancer, and brain cancer. Thus intense efforts have been made to inhibit the activity of EGFR by designing antibodies against the ligand binding domains (cetuximab and panitumumab) or small molecules against the tyrosine kinase domain (erlotinib, gefitinib, and lapatinib). Although targeting membrane-bound EGFR has shown benefit, a new and emerging role for EGFR is now being elucidated. In this review we will summarize the current knowledge of the nuclear EGFR signaling network, including how it is trafficked to the nucleus, the functions it serves in the nucleus, and how these functions impact cancer progression, survival, and response to chemotherapeutics.read more
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Emerging functions of the EGFR in cancer
TL;DR: The canonical ligand‐induced EGFR signaling pathway is reviewed, with particular emphasis to its regulation by endocytosis and subversion in human tumors, and the most recent advances in uncovering noncanonical EGFR functions in stress‐induced trafficking, autophagy, and energy metabolism are focused on.
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Targeting the ERBB family in cancer: couples therapy
TL;DR: The preclinical and clinical performance of these dual-targeting approaches are described, the key mechanisms that mediate their increased efficacy and highlights areas for ongoing investigation are discussed.
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Multicenter Phase II Study of Neoadjuvant Lapatinib and Trastuzumab With Hormonal Therapy and Without Chemotherapy in Patients With Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer: TBCRC 006
Mothaffar F. Rimawi,Ingrid A. Mayer,Andres Forero,Rita Nanda,MP Goetz,Angel Rodriguez,Anne Pavlick,Tao Wang,Susan G. Hilsenbeck,Carolina Gutierrez,Rachel Schiff,C. Kent Osborne,Jenny C. Chang +12 more
TL;DR: The hypothesis that selected patients with HER2-positive tumors may not need chemotherapy, and more-complete blockade of HER receptors and ER is an effective strategy worthy of further study is supported.
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Nuclear EGFR as a molecular target in cancer
TL;DR: The current knowledge of how nuclear EGFR enhances resistance to cancer therapeutics is discussed, in addition to highlighting ways to targetnuclear EGFR as an anti-cancer strategy in the future.
Journal ArticleDOI
Nuclear functions and subcellular trafficking mechanisms of the epidermal growth factor receptor family
TL;DR: 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 are summarized.
References
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Journal ArticleDOI
Inducible nitric oxide synthase (iNOS) in tumor biology: the two sides of the same coin
TL;DR: The dual actions of iNOS are summarized as simultaneous tumor promoter and suppressor for nitric oxide synthase, which has a potentially cytotoxic/cytostatic effect upon tumor cells.
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Importin Beta: Conducting a Much Larger Cellular Symphony
Amnon Harel,Douglass J. Forbes +1 more
TL;DR: Importin beta plays a role in transducing damage signals from the axons of injured neurons back to the cell body, although it is also possible that one of importin beta's relatives, the karyopherin family of proteins, manages this checkpoint.
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Tyrosine phosphorylation controls PCNA function through protein stability.
Shao Chun Wang,Yusuke Nakajima,Yusuke Nakajima,Yung Luen Yu,Weiya Xia,Chun Te Chen,Cheng Chieh Yang,Eric W. McIntush,Long Yuan Li,Long Yuan Li,David H. Hawke,Ryuji Kobayashi,Mien Chie Hung +12 more
TL;DR: A novel nuclear mechanism linking tyrosine kinase receptor function with the regulation of the PCNA sliding clamp is identified, which is better correlated with poor survival of breast cancer patients, as well as nuclear EGFR in tumours, than is the total PCNA level.
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Nuclear EGFR contributes to acquired resistance to cetuximab.
TL;DR: It is demonstrated that cetuximab-resistant cells overexpress HER family ligands including epidermal growth factor (EGF), amphiregulin, heparin-binding EGF and β-cellulin, which suggest that nuclear expression of EGFR may be an important molecular determinant of resistance to cetUXimab therapy.
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Binding at and transactivation of the COX-2 promoter by nuclear tyrosine kinase receptor ErbB-2
Shao Chun Wang,Huang-Chun Lien,Weiya Xia,I. Fen Chen,Hui-Wen Lo,Zhiqin Wang,Mohamed Ali-Seyed,Dung Fang Lee,Dung Fang Lee,Geoffrey Bartholomeusz,Fu Ou-Yang,Dipak Giri,Mien Chie Hung +12 more
TL;DR: It is reported that ErbB-2 is also expressed in the nucleus in cultured cells as well as primary tumor tissues and the function of Erb B-2 as a transcriptional regulator is identified.