scholarly journals Receptor tyrosine kinase signaling required for integrin alpha v beta 5-directed cell motility but not adhesion on vitronectin.

1994 ◽  
Vol 127 (3) ◽  
pp. 859-866 ◽  
Author(s):  
R L Klemke ◽  
M Yebra ◽  
E M Bayna ◽  
D A Cheresh
Keyword(s):  
Cell Migration ◽  
Tyrosine Kinase ◽  
Cell Motility ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
De Novo ◽  
Growth Factor Receptor ◽  
Dependent Manner ◽  
Pkc Activation

FG human pancreatic carcinoma cells adhere to vitronectin using integrin alpha v beta 5 yet are unable to migrate on this ligand whereas they readily migrate on collagen in an alpha 2 beta 1-dependent manner. We report here that epidermal growth factor receptor (EGFR) activation leads to de novo alpha v beta 5-dependent FG cell migration on vitronectin. The EGFR specific tyrosine kinase inhibitor tyrphostin 25 selectively prevents EGFR autophosphorylation thereby preventing the EGF-induced FG cell migration response on vitronectin without affecting constitutive migration on collagen. Protein kinase C (PKC) activation also leads to alpha v beta 5-directed motility on vitronectin; however, this is not blocked by tyrosine kinase inhibitors. In this case, PKC activation appears to be associated with and downstream of EGFR signaling since calphostin C, an inhibitor of PKC, blocks FG cell migration on vitronectin induced by either PKC or EGF. These findings represent the first report implicating a receptor tyrosine kinase in a specific integrin mediated cell motility event independent of adhesion.

Targeting epidermal growth factor receptor pathway with irreversible tyrosine kinase inhibitor

2019 ◽  
Vol 44 (1) ◽  
pp. 62-69
Author(s):  
Fatma Sagir ◽  
Asuman Demiroglu-Zergeroglu
Keyword(s):  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Central Anatolia ◽  
Pcr Analysis ◽  
Dependent Manner ◽  
Rt Pcr ◽  
Proliferative Effect

Abstract Background Malignant mesothelioma (MM) is an endemic disease around central Anatolia region in Turkey, where people are exposed to erionite- and asbestos-contaminated soil. Aberrant EGFR signalling has implicated in several cancers including MMs. Tyrosine kinase inhibitors are new treatment options harbouring deregulated signalling network components. In this study, we aimed to investigate anti-proliferative effect of CL-387,785 in MM cells. Materials and methods Alteration of cell proliferation was evaluated with using MTS assay. Profile of EGFR, ERK, AKT, JNK and p38 proteins and ELK-1, JUN, STAT1, STAT3 and STAT5 genes were analysed by western blot and RT-PCR, respectively. Results Viability of MM cells was inhibited in dose- and time-dependent manner. CL-387,785 affected MM cells earlier and at higher extent compared to the mesothelial cells. CL-387,785 treatments suppressed EGF-induced phosphorylation of EGFR, ERK, AKT, STAT3 and STAT5 but not SAPK/JNK and p38 in SPC212 cells. RT-PCR analysis showed that expression of p21 increased, while Cyclin D and c-jun expressions decreased in SPC212 cells. However, ELK-1, STAT3 and STAT5, expressions did not change. Conclusion Our results propose that CL-387,785 could be an efficacious agent in the treatment of MMs with uncontrolled EGFR signalling.

Successful retreatment with erlotinib after erlotinib-related interstitial lung disease

2021 ◽  
pp. 030089162110200
Author(s):  
Haci M. Turk ◽  
Mustafa Adli ◽  
Melih Simsek ◽  
Altay Aliyev ◽  
Mehmet Besiroglu
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Interstitial Lung Disease ◽  
Epidermal Growth Factor ◽  
Tyrosine Kinase ◽  
Lung Disease ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Epidermal Growth

Background: Epidermal growth factor receptor tyrosine kinase inhibitors are effectively being used in the treatment of non-small cell lung cancer. Although most of their adverse effects are mild to moderate, they occasionally can cause life-threatening interstitial lung disease. We aimed to present a case of lung adenocarcinoma successfully re-treated with erlotinib after recovery with effective treatment of erlotinib-induced interstitial lung disease. Case description: A 54-year-old nonsmoking woman was diagnosed with metastatic adenocarcinoma of the lung. After progression with first-line chemotherapy, erlotinib 150 mg daily was initiated. On the 45th day of erlotinib treatment, interstitial lung disease occurred and erlotinib was discontinued. Clinical improvement was achieved with dexamethasone treatment and erlotinib was re-initiated. Ten weeks after re-initiation of erlotinib, 100 mg daily partial response was observed. Conclusions: Incidence of interstitial lung disease is higher in men, smokers, and patients with pulmonary fibrosis. Interstitial lung disease radiologically causes ground-glass opacity and consolidation. The physician should quickly evaluate new respiratory symptoms in patients treated with epidermal growth factor receptor tyrosine kinase inhibitors, discontinue the epidermal growth factor receptor tyrosine kinase inhibitor treatment, and initiate corticosteroids if clinical diagnosis is interstitial lung disease.

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