scholarly journals MicroRNA Expression Profiling of Lung Cancer with Differential Expression of the RON Receptor Tyrosine Kinase

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Huilin Ou ◽  
Keda Chen ◽  
Hongcheng Wu
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Cell Lung Cancer ◽  
Receptor Tyrosine Kinase ◽  
Mapk Signaling ◽  
Differentially Expressed ◽  
Biological Behavior ◽  
Cancer Type ◽  
Mesenchymal Transition ◽  
Ron Receptor

Background. The Ron receptor tyrosine kinase (RON) can act as a protooncogene and may play a prominent role in the initiation and development of lung cancer. microRNAs (miRNA) are master regulators of gene expression through direct or indirect regulation, and impact all aspects of cell biology. Methods. Nonsmall-cell lung cancer (NSCLC) samples and small-cell lung cancer (SCLC) were stratified based on RON expression to identify miRNA profiles associated with RON expression levels, differentially expressed miRNA regulated by RON were screened out, and their biological behavior was analyzed. Results. miRNA expression was most significantly affected by cancer type, and we found 85 miRNAs that were significantly differentially expressed between NSCLC and SCLC. There were 46 miRNAs differentially expressed between high RON expressing NSCLC compared to low RON expressing NSCLC. Biological processes and pathways found to be significantly influenced by RON expression included epithelial-mesenchymal transition (EMT) and activation of the PI3K-Akt and MAPK signaling pathways. Conclusions. These data may provide the basis for a novel strategy to characterize lung cancer by RON expression and microRNA genotyping.

scholarly journals Functional Analyses of Mutations in Receptor Tyrosine Kinase Genes in Non–Small Cell Lung Cancer: Double-Edged Sword of DDR2

2016 ◽  
Vol 22 (14) ◽  
pp. 3663-3671 ◽  
Author(s):  
Masato Terashima ◽  
Yosuke Togashi ◽  
Katsuaki Sato ◽  
Hiroshi Mizuuchi ◽  
Kazuko Sakai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Receptor Tyrosine Kinase ◽  
Small Cell ◽  
Small Cell Lung ◽  
Functional Analyses

scholarly journals Receptor Tyrosine Kinase and p16/CDKN2 Expression in a Case of Tripe Palms Associated with Non-Small-Cell Lung Cancer

Dermatology ◽  
1999 ◽  
Vol 199 (4) ◽  
pp. 290-295 ◽  
Author(s):  
G. Krähn ◽  
K.M. Greulich ◽  
G. Bezold ◽  
C. Dieterle ◽  
H. Wolff ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Receptor Tyrosine Kinase ◽  
Small Cell ◽  
Small Cell Lung

Activation of HGF/c-Met pathway contributes to the reactive oxygen species generation and motility of small cell lung cancer cells

2007 ◽  
Vol 292 (6) ◽  
pp. L1488-L1494 ◽  
Author(s):  
Ramasamy Jagadeeswaran ◽  
Sujatha Jagadeeswaran ◽  
Vytas P. Bindokas ◽  
Ravi Salgia
Keyword(s):  
Lung Cancer ◽  
Reactive Oxygen Species ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Receptor Tyrosine Kinase ◽  
Small Cell ◽  
Oxygen Species ◽  
Small Cell Lung ◽  
Met Receptor Tyrosine Kinase

Small cell lung cancer (SCLC) is a difficult disease to treat and sometimes has overexpression or mutation of c-Met receptor tyrosine kinase. The effects of c-Met/hepatocyte growth factor (c-Met/HGF, ligand for c-Met) on activation of reactive oxygen species (ROS) was determined. HGF stimulation of c-Met-overexpressing H69 SCLC cells (40 ng/ml, 15 min) resulted in an increase of ROS, measured with fluorescent probe 2′-7′-dichlorofluorescein diacetate (DCFH-DA) or dihydroethidine (DHE) but not in c-Met-null H446 cells. ROS was increased in juxtamembrane (JM)-mutated variants (R988C and T1010I) of c-Met compared with wild-type c-Met-expressing cells. ROS was significantly inhibited by preincubation of SCLC cells with pyrrolidine dithiocarbamate (PDTC, 100 μM) and/or SU11274 (small molecule c-Met tyrosine kinase inhibitor, 2 μM) for 3 h. PDTC and SU11274 also abrogated the HGF proliferative signal and cell motility in a cooperative fashion. H2O2 treatment of SCLC cells (over 15 min) led to phosphorylation of c-Met receptor tyrosine kinase and further upregulated downstream phosphorylation of phospho-AKT, ERK1/2, and paxillin in a dose-dependent manner (125 μM to 500 μM). c-Met is an important target in lung cancer, and the pathways responsible for ROS generation together may provide novel therapeutic intervention.

scholarly journals RADI-19. The Incidence of New Brain Metastases in Patients with Non-Small Cell Lung Cancer Following Discontinuation of Systemic Therapy

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii22-iii22
Author(s):  
Dennis London ◽  
Dev Patel ◽  
Bernadine Donahue ◽  
Ralph Navarro ◽  
Jason Gurewitz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Receptor Tyrosine Kinase ◽  
Systemic Therapy ◽  
Cox Regression ◽  
Small Cell ◽  
Small Cell Lung

Abstract Purpose Patients with non-small cell lung cancer (NSCLC) metastatic to the brain increasingly are living longer due to improvements in systemic therapy and local modalities. The risk of new brain metastases when these patients stop systemic therapy is unknown. Recognizing patterns of new tumor occurrence is necessary to determine the frequency of follow-up and the need for further treatment. Methods We included patients in a prospective registry who had non-small cell lung cancer (NSCLC) brain metastases, discontinued systemic therapy for at least 90 days, and underwent active surveillance. 63 patients with 73 off-periods were studied. The risk factors for the development of new tumors were determined using Cox regression and multi-state Markov modeling. Results The median time to new brain metastases off systemic therapy was 16.0 months. The probability of developing an additional new tumor at 6, 12, and 18 months was 26%, 40%, and 53%, respectively. There were no additional new tumors 22 months after stopping therapy. Patients who discontinued therapy due to intolerance or progression of the disease and those with mutations in RAS or receptor tyrosine kinase pathways (e.g. KRAS, EGFR) were more likely to develop new tumors (HR: 2.21, 95% CI: 1.25–3.91, p=6.3 x 10–3; HR: 2.03, 95% CI: 1.09–3.77, p=0.026, respectively). Conclusion The rate of new brain metastases from NSCLC in patients off systemic therapy decreases over time and is uncommon 2 years after cessation of cancer therapy. Patients who stop therapy due to toxicity or who have RAS or receptor tyrosine kinase pathway mutations have a higher rate of new metastases and should be followed more closely.

scholarly journals STYK1/NOK Promotes Metastasis and Epithelial-Mesenchymal Transition in Non-small Cell Lung Cancer by Suppressing FoxO1 Signaling

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuanyang Lai ◽  
Fang Lin ◽  
Xuejiao Wang ◽  
Jiao Zhang ◽  
Jinghua Xia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Tyrosine Kinase ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mesenchymal Transition

AimsSerine/threonine/tyrosine kinase 1 (STYK1) has been previously shown to have oncogenic properties, and emerging evidence suggests that STYK1 expression correlates with epithelial-mesenchymal transition (EMT). However, the mechanism of STYK1 involvement in oncogenesis remains unknown. The present study aimed to elucidate how STYK1 expression level relates to the metastasis, migration, invasion, and EMT in non-small cell lung cancer (NSCLC) and to determine the molecular mechanism of STYK1 effects.MethodsSerine/threonine/tyrosine kinase 1 (STYK1) expression level and its relationship with the prognosis of NSCLC were determined using the ONCOMINE database and clinical cases. Non-small cell lung cancer cell lines with the overexpression or knockdown of STYK1 were established to determine whether STYK1 promotes cell migration, invasion, and EMT in vitro and in vivo. In addition, a constitutively active FoxO1 mutant (FoxO1AAA) was used to examine the role of FoxO1 in the STYK1-mediated upregulation of metastasis and EMT in NSCLC.ResultsSerine/threonine/tyrosine kinase 1 (STYK1) was upregulated in NSCLC tissues and cell lines, and its overexpression correlated with poor prognosis in patients with NSCLC after surgery. Enhanced expression of STYK1 potentiated the migration, invasion, and EMT in SW900 cells, thereby promoting metastasis, whereas knockdown of STYK1 inhibited these cellular phenomena in Calu-1 cells. Furthermore, STYK1 expression was positively related to the level of phosphorylated-FoxO1, whereas the constitutively active FoxO1 mutant protected against the positive effect of STYK1 overexpression on cell migration, invasion, and EMT.ConclusionSerine/threonine/tyrosine kinase 1 (STYK1) was upregulated in NSCLC and correlated with poor clinical outcomes. In addition, STYK1 suppressed FoxO1 functions, thereby promoting metastasis and EMT in NSCLC.

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