By crossing Twist1a-ERT2 with xmrk (a homolog of hyperactive form of epidermal growth factor receptor) transgenic zebrafish, which develops hepatocellular carcinoma, ~80% of the double transgenic zebrafish showed spontaneous cell dissemination of mCherry-labelled hepatocytes from the liver to the entire abdomen region and the tail region.
Using a combination of high-content imaging and a mammalian membrane two-hybrid protein-protein interaction method, we identified eight novel interaction partners of EGFR, of which half strongly interacted with oncogenic, hyperactiveEGFR variants.
In this article, we summarize pulmonary fibrotic changes observed after a SARS-CoV infection, discuss the extent to which other respiratory viruses induce fibrosis, describe available animal models to study the development of SARS-CoV induced fibrosis and review evidence that pulmonary fibrosis is caused by a hyperactive host response to lung injury mediated by epidermal growth factor receptor (EGFR) signaling.
Treatment with inhibitors of Src (SU6656) or EGFR (AG1478) reduced EGFR phosphorylation and downstream signaling which resulted in the inhibition of the OVA-induced inflammatory cell influx in bronchoalveolar lavage fluid (BALF), perivascular and peribronchial inflammation, fibrosis, goblet cell hyper/metaplasia and airway hyper-responsiveness.
Using our previously established xmrk transgenic zebrafish, hepatocellular carcinoma (HCC) was generated by induced expression of xmrk, which encoded a hyperactive epidermal growth factor receptor (EGFR) homolog, and regressed by suppression of xmrk expression.
A constitutive activation of protein kinase B (AKT) in a hyper-phosphorylated status at Ser473 is one of the hallmarks of anti-EGFR therapy-resistant colorectal cancer (CRC).
Using non-small cell lung carcinoma (NSCLC) cells harboring the erlotinib-sensitizing Epidermal Growth Factor Receptor (EGFR) exon 19 mutation delE746-A750, we developed erlotinib-refractory derivatives in which hyperactive Insulin-like Growth Factor-1 Receptor (IGF-1R) signaling associated with enrichment in epithelial-to-mesenchymal transition (EMT)-related morphological and transcriptional features.
Western blot analysis showed that these EGFR mutations enhanced cell growth and invasion via constitutive and hyperactive tyrosine phosphorylation and led to the activation of mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3 (STAT3) and Akt pathways.
Malignant peripheral nerve sheath tumors (MPNSTs), driven in part by hyperactive Ras and epidermal growth factor receptor (EGFR) signaling, are often incurable.
Abnormalities in EGF-EGFR signaling, such as mutations that render the EGFRhyperactive or cause overexpression of the wild-type receptor, have been found in a broad range of cancers, including carcinomas of the lung, breast, and colon.
We postulate that negative regulation of the PI 3-K/Akt pathway by PTEN may modulate the effects of the hyperactiveepidermal growth factor receptor/mitogen-activated protein kinase pathway, contributing to the low proliferation and dysfunctional differentiation of laryngeal papillomas.