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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c-erbB-3: a nuclear protein in mammary epithelial cells
TL;DR: Using immunofluorescence, high levels of c-erbB-3 were found within the nuclei of MTSV1-7 immortalized nonmalignant human mammary epithelial cells, suggesting that c- Derbyshire shuttles between nuclear and nonnuclear compartments in these cells.
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Radiation-induced caveolin-1 associated EGFR internalization is linked with nuclear EGFR transport and activation of DNA-PK.
TL;DR: Ionizing radiation resulted in src kinase stabilization, activation and subsequent src mediated caveolin-1 Y14- and EGFR Y845-phosphorylations, which resulted in an enhanced residual DNA-damage as quantified 24 h after irradiation and increased radiosensitivity.
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Nuclear epidermal growth factor receptor (EGFR) interacts with signal transducer and activator of transcription 5 (STAT5) in activating Aurora-A gene expression
Liang Yi Hung,Joseph T. Tseng,Yi Chao Lee,Weiya Xia,Ying Nai Wang,Min Li Wu,Yu Hsuan Chuang,Chein Hsien Lai,Wen Chang Chang +8 more
TL;DR: This study proposes that the nuclear EGFR associates with STAT5 to bind and increase Aurora-A gene expression, which ultimately may lead to chromosome instability and tumorigenesis.