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
Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib
Kwak Eunice L,Raffaella Sordella,Daphne W. Bell,Godin-Heymann Nadia G,Ross A. Okimoto,Brian W. Brannigan,Patricia L. Harris,David R. Driscoll,Panos Fidias,Thomas J. Lynch,Sridhar K. Rabindran,John P. McGinnis,Allan Wissner,Sreenath V. Sharma,Kurt J. Isselbacher,Jeffrey Settleman,Daniel A. Haber +16 more
TL;DR: These findings suggest that one of these, HKI-272, may prove highly effective in the treatment of EGFR-mutant NSCLCs, including tumors that have become resistant to gefitinib or erlotinib.
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γ-Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase
TL;DR: A subsequent cleavage by γ-secretase that releases the ErbB-4 intracellular domain from the membrane and facilitates its translocation to the nucleus is reported.
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Roles of Aurora Kinases in Mitosis and Tumorigenesis
TL;DR: Both the expression level and the kinase activity of Aurora kinases are found to be up-regulated in many human cancers, indicating that these kinases might serve as useful targets for the development of anticancer drugs.
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Mechanisms of acquired resistance to cetuximab: role of HER (ErbB) family members.
Deric L. Wheeler,Shyhmin Huang,Tim J. Kruser,Meghan M. Nechrebecki,Eric A. Armstrong,Sergi Benavente,Vinai Gondi,Kun-Tai Hsu,Paul M. Harari +8 more
TL;DR: The data suggest that acquired resistance to cetuximab is accompanied by dysregulation of EGFR internalization/degradation and subsequent EGFR-dependent activation of HER3, suggesting a rationale for the clinical evaluation of combinatorial anti-HER targeting approaches in tumors manifesting acquired resistance.
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Radiation-induced epidermal growth factor receptor nuclear import is linked to activation of DNA-dependent protein kinase
Klaus Dittmann,Claus Mayer,Birgit Fehrenbacher,Martin Schaller,Uma Raju,Luka Milas,David J. Chen,Rainer Kehlbach,H. Peter Rodemann +8 more
TL;DR: The data implicate a novel function of the EGFR during DNA repair processes and radiation-induced activation of DNA-PK, inhibited DNA repair, and increased radiosensitivity of treated cells.