The Role of Epidermal Growth Factor Receptor in Cancer Metastasis and Microenvironment

Sasaki, Takuma; Kuniyasu, Hiroki; Yamashita, Yuichi

doi:10.1155/2013/546318

Cited by 245 publications

(176 citation statements)

References 73 publications

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“…In addition to their function in normal development, aberrant expression of EGFR is involved in abnormal cell proliferation, reduced apoptosis, cell migration, metastasis, and angiogenesis in cancer patients (1,2). Activation of EGFR converts extracellular stimulations into intracellular signals to regulate cellular responses through protein modifications.…”

Section: Introductionmentioning

confidence: 99%

PRMT1-mediated methylation of the EGF receptor regulates signaling and cetuximab response

Liao

Hsu

Xia

et al. 2015

Journal of Clinical Investigation

120

121

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R e s e a R c h a R t i c l e4 5 3 0 jci.org Volume 125 Number 12 December 2015 ing activation of HER2 or MET signaling, mutation of PIK3CA and BRAF, or expression status of PTEN, but retrospective analyses revealed inconsistent and controversial findings (16). So far, the most accepted predictive marker for poor cetuximab response is mutant KRAS status, due to its association with poor survival rate under cetuximab treatment in colorectal cancer clinical trials (17)(18)(19)(20). Therefore, American Society of Clinical Oncology recommended cetuximab treatment for only patients with WT KRAS (21). However, there is increasing evidence showing that WT KRAS is not sufficient to confer sensitivity to cetuximab (22)(23)(24), and some patients with mutant KRAS are still sensitive to cetuximab (16,(25)(26)(27)(28). These findings suggest that further investigation into the underlying mechanisms of cetuximab resistance and identification of a better predictor for cetuximab response are ing of chemotherapeutic agents have improved the response and survival rate of colorectal patients. Currently, rational targeting of molecular signaling pathways that are involved in the etiology of malignancies is one of the most promising strategies in novel anticancer drug development (13). Owing to the role of EGFR in tumorigenesis, new classes of drugs that target EGFR are among the most clinically advanced molecular-targeted therapies. Although EGFR tyrosine kinase inhibitors combined with chemotherapy presented severe toxicity and limited effect (14), the combination of EGFR monoclonal antibody, such as cetuximab and panitumumab, with chemotherapy has shown efficacy in colorectal cancer treatment (15). Unfortunately, resistance to EGFR-targeted therapy has recently been observed. Many mechanisms have been proposed to explain the poor response to cetuximab, includ-

show abstract

Section: Introductionmentioning

confidence: 99%

PRMT1-mediated methylation of the EGF receptor regulates signaling and cetuximab response

Liao

Hsu

Xia

et al. 2015

Journal of Clinical Investigation

120

121

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show abstract

“…The structure of all receptor tyrosine kinases consists of three parts: an extracellular ligand-binding domain, a transmembrane segment, and an intracellular tyrosine kinase domain with a carboxyl terminal segment. Ligand-driven signaling of EGFR plays an important role in cell growth as well as proliferation and cell division, and changes in EGFR properties such as overexpression and mutation have been implicated in different cancer types (2,3). Therefore, understanding EGFR oligomerization and dynamics in the plasma membrane and its role in regulation of EGFR signaling is important to elucidate its role in cancer progression and for the development of new anti-cancer therapies.…”

Section: Introductionmentioning

confidence: 99%

The Epidermal Growth Factor Receptor Forms Location-Dependent Complexes in Resting Cells

Yavas

Macháň

Wohland

2016

Biophysical Journal

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The epidermal growth factor receptor (EGFR) is a prototypical receptor tyrosine kinase involved in cell growth and proliferation and associated with various cancers. It is commonly assumed that after activation by binding of epidermal growth factor to the extracellular domain it dimerizes, followed by autophosphorylation of tyrosine residues at the intracellular domain. However, its oligomerization state before activation is controversial. In the absence of ligands, EGFR has been found in various, inconsistent amounts of monomeric, inactive dimeric, and oligomeric forms. In addition, evidence suggests that the active conformation is not a simple dimer but contains higher oligomers. As experiments in the past have been conducted at different conditions, we investigate here the influence of cell lines (HEK293, COS-7, and CHO-K1), temperature (room temperature and 37 C), and membrane localization on the quantitation of preformed dimers using SW-FCCS, DC-FCCS, quasi PIE-FCCS, and imaging FCCS. While measurement modality, temperature, and localization on upper or lower membranes have only a limited influence on the dimerization amount observed, the cell line and location to periphery versus center of the cell can change dimerization results significantly. The observed dimerization amount is strongly dependent on the expression level of endogenous EGFR in a cell line and shows a strong cell-to-cell variability even within the same cell line. In addition, using imaging FCCS, we find that dimers have a tendency to be found at the periphery of cells compared to central positions.

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“…Members of Dok family of protein have three domains: A N terminal homology domain, a phospho tyrosine bonding domain and a C terminal proline rich domain with few tyrosine residues. This C-terminal with SH2 and SH3 domain recruits the signaling intermediates on growth factor stimulation [1][2][3][4]. Epidermal growth factor receptor signaling is essentially been viewed as an Important player in shaping cancer microenvironment [4] and an important target for cancer therapy [5].…”

Section: Biology Of Dok2mentioning

confidence: 99%

“…This C-terminal with SH2 and SH3 domain recruits the signaling intermediates on growth factor stimulation [1][2][3][4]. Epidermal growth factor receptor signaling is essentially been viewed as an Important player in shaping cancer microenvironment [4] and an important target for cancer therapy [5]. Dok1-3 are reported to modulate epidermal growth factor receptor [6,7] as well as platelet derived growth factor receptor and associated signaling pathways [1,8,9].…”

Section: Biology Of Dok2mentioning

confidence: 99%

Significance of Dok2 Protein in Cancer Prognosis and Progression

Rp¹,

Pb²

2017

J Mol Genet Med

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Cancer is the most leading cause of deaths worldwide. Despite present understanding and experimental advancements, the morbidity and mortality still remain high. Dok2 have been visualized as a key player in multiple biological processes as inflammation, differentiation, cellular migration and even as an important marker for tumor progression. Recent reports have vividly discussed the regulatory aspects and prognostic aspects of Dok2. Here, we sought to summarize the recent shreds of evidence of Dok2 involvement in carcinogenesis. Dok2 represents an attractive marker for cancer progression and represents a valuable therapeutic target.

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The Role of Epidermal Growth Factor Receptor in Cancer Metastasis and Microenvironment

Cited by 245 publications

References 73 publications

PRMT1-mediated methylation of the EGF receptor regulates signaling and cetuximab response

PRMT1-mediated methylation of the EGF receptor regulates signaling and cetuximab response

The Epidermal Growth Factor Receptor Forms Location-Dependent Complexes in Resting Cells

Significance of Dok2 Protein in Cancer Prognosis and Progression

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