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
Citations
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Adaptive Upregulation of EGFR Limits Attenuation of Tumor Growth by Neutralizing IL6 Antibodies, with Implications for Combined Therapy in Ovarian Cancer
Carla Milagre,Ganga Gopinathan,Gemma Everitt,Richard G. Thompson,Hagen Kulbe,Haihong Zhong,Robert E. Hollingsworth,Richard Grose,David D.L. Bowtell,Daniel Hochhauser,Frances R. Balkwill +10 more
TL;DR: Preclinical rationale to combine anti-IL6 and gefitinib to treat patients with advanced stage ovarian cancer is offered, based on the finding that neutralizing antibodies to IL6 and STAT3 inhibition are sufficient to upregulate the EGFR pathway in high-grade serous and other ovarian cancer cells.
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The receptor tyrosine kinase AXL mediates nuclear translocation of the epidermal growth factor receptor
Toni M. Brand,Mari Iida,Kelsey L. Corrigan,Cara M. Braverman,John P. Coan,Bailey Flanigan,Andrew P. Stein,Ravi Salgia,Jana Rolff,Randall J. Kimple,Deric L. Wheeler +10 more
TL;DR: A previously unrecognized role for AXL is uncovered in regulating the nuclear translocation of EGFR and it is suggested that AXL-mediated SFK and NRG1 expression promote this process.
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Paradoxical roles of dual oxidases in cancer biology.
Andrew C. Little,Arvis Sulovari,Karamatullah Danyal,David E. Heppner,David J. Seward,Albert van der Vliet +5 more
TL;DR: A better understanding of mechanisms that regulate DUOX and the functional consequences of DUOX silencing in cancer may offer valuable new diagnostic insights and novel therapeutic opportunities.
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In silico prediction of synthetic lethality by meta-analysis of genetic interactions, functions, and pathways in yeast and human cancer.
TL;DR: An approach named MetaSL is proposed for predicting yeast SL, which integrates 17 genomic and proteomic features and the outputs of 10 classification methods and achieves the highest area under the Receiver Operating Characteristics (ROC) curve (AUC) of 87.1% among all competitors on yeast data.
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Design of smart GE11-PLGA/PEG-PLGA blend nanoparticulate platforms for parenteral administration of hydrophilic macromolecular drugs: synthesis, preparation and in vitro/ex vivo characterization
Barbara Colzani,Giovanna Speranza,Rossella Dorati,Bice Conti,Tiziana Modena,Giovanna Bruni,Elisa Zagato,Lotte Vermeulen,George R. Dakwar,Kevin Braeckmans,Ida Genta +10 more
TL;DR: EGFR-targeted polylactide-co-glycolide (PLGA) nanoparticles made by a blend of two different PLGA-based polymers can be considered highly promising as smart nanoparticulate platforms for the treatment of diseases characterized by EGFR overexpression by parenteral administration.
References
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Journal ArticleDOI
Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications
Therese Sørlie,Charles M. Perou,Robert Tibshirani,Turid Aas,Stephanie Geisler,Hilde Johnsen,Trevor Hastie,Michael B. Eisen,Matt van de Rijn,Stefanie S. Jeffrey,T. Thorsen,Hanne Quist,John C. Matese,Patrick O. Brown,David Botstein,Per Eystein Lønning,Anne Lise Børresen-Dale +16 more
TL;DR: Survival analyses on a subcohort of patients with locally advanced breast cancer uniformly treated in a prospective study showed significantly different outcomes for the patients belonging to the various groups, including a poor prognosis for the basal-like subtype and a significant difference in outcome for the two estrogen receptor-positive groups.
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Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells
Axel Ullrich,Lisa M. Coussens,Joel S. Hayflick,Thomas J. Dull,Alane M. Gray,A W Tam,Jeffrey E. Lee,Yosef Yarden,Towia A. Libermann,Joseph Schlessinger +9 more
TL;DR: The complete 1,210-amino acid sequence of the human epidermal growth factor (EGF) receptor precursor, deduced from cDNA clones derived from placental and A431 carcinoma cells, reveals close similarity between the entire predicted ν-erb-B mRNA oncogene product and the receptor transmembrane and cytoplasmic domains.
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Immunohistochemical and Clinical Characterization of the Basal-Like Subtype of Invasive Breast Carcinoma
Torsten O. Nielsen,Forrest D. Hsu,Kristin C. Jensen,Maggie C.U. Cheang,Gamze Karaca,Zhiyuan Hu,Tina Hernandez-Boussard,Chad A. Livasy,Dave Cowan,Lynn G. Dressler,Lars A. Akslen,Joseph Ragaz,Allen M. Gown,C. Blake Gilks,Matt van de Rijn,Charles M. Perou +15 more
TL;DR: A panel of four antibodies (ER, HER1, HER2, and cytokeratin 5/6) can accurately identify basal-like tumors using standard available clinical tools and shows high specificity.
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Isolation of a Mouse Submaxillary Gland Protein Accelerating Incisor Eruption and Eyelid Opening in the New-born Animal
TL;DR: The isolation of the factor responsible for the earlier development of the incisors and eyelids is reported here, a heat-stable, nondialysable, antigenic protein, whose most distinctive chemical characteristic is the absence of phenylalanine and lysine.
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Nuclear localization of EGF receptor and its potential new role as a transcription factor
Shiaw Yih Lin,Keishi Makino,Weiya Xia,Angabin Matin,Yong Wen,Ka Yin Kwong,Lilly Y.W. Bourguignon,Mien Chie Hung +7 more
TL;DR: It is demonstrated that nuclear EGFR is strongly correlated with highly proliferating activities of tissues and associated with promoter region of cyclin D1 in vivo, suggesting that EGFR might function as a transcription factor to activate genes required for highly proliferationating activities.