STEM-01. PHAGE DISPLAY BIOPANNING IDENTIFIES AMOT REGULATING CELL MOTILITY OF BRAIN METASTATIC STEM-LIKE CELLS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi21-vi21
Author(s):  
Chunhua She ◽  
JongMyung Kim ◽  
Marine Potez ◽  
James Liu
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Brain Tumors ◽  
Cell Motility ◽  
Primary Lung Cancer ◽  
In Silico Analysis ◽  
Intracranial Lesions ◽  
Phage Display Biopanning ◽  
Silico Analysis ◽  
E Cadherin

Abstract OBJECTIVE Metastatic brain tumors (MBTs) are the most common type of malignant brain tumors. Due to the deviation of MBTs from the parental tumors, the effective therapies for primary tumors often are not useful in brain metastases. Even more new intracranial lesions were developed though the primary lesion was under control. The model of brain metastatic stem-like cells (BMSCs) could partially explain the progression of intracranial lesions. Here we aimed to explore the biological behavior in cell motility of BMSCs and understand the potential mechanisms. METHODS In vitro and in vivo phage display biopanning strategies were used to isolate dodecapeptides that specifically target BMICs by selecting against primary lung cancer cells and normal brain cells. In silico analysis was used to derive specific protein targets in BMICs. Potential targets were narrowed down through analysis in patient databases and verified for their presence in BMIC through RT-PCR. Cell migration and adhesion in BMICs were analyzed using Transwell, scratch, and adhesion assays. Protein expression and cell morphology were detected by immunofluorescence. Immune blot was performed to detect the epithelial-mesenchymal related molecules and explore protein-protein interactions. RESULTS In silico analysis of BMSCs specific peptides revealed Angiomotin (Amot) as a potential target in BMSCs. Amot was found to be overexpressed in BMSCs compared to primary lung cancer cells. Kaplan-Meier analysis demonstrated Amot was negatively correlated with overall survival among lung adenocarcinoma patients. Functionally, knockdown of AMOT in BMSCs decreased the capability of cell migration and adhesion by reduced active Cdc42/Rac1 signals caused by downregulation of E-Cadherin. Amot was found to maintain the E-Cadherin in BMSCs through reducing ubiquitination of E-Cadherin. CONCLUSIONS Amot plays a role in promoting migration and adhesion in BMSCs through preservation of E-cadherin.

scholarly journals BSCI-06. Phage display biopanning identifies Amot regulating cell motility in brain metastasis-initiating cells

2021 ◽  
Vol 3 (Supplement_3) ◽  
pp. iii2-iii2
Author(s):  
Chunhua She ◽  
Marine Potez ◽  
JongMyung Kim ◽  
James Liu
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Brain Metastasis ◽  
Brain Tumors ◽  
Cell Motility ◽  
Primary Lung Cancer ◽  
In Silico Analysis ◽  
Phage Display Biopanning ◽  
Silico Analysis ◽  
E Cadherin

Abstract Objective Metastatic brain tumors (MBTs) are the most common type of malignant brain tumors. Due to the deviation of MBTs from the parental tumors, the effective therapies for primary tumors often are not working in brain metastases. Even more new intracranial lesions were developed though the primary lesion was controlled. The occurrence of brain metastasis-initiating cells (BMICs) suggested the possibility of its spread intracranially. Here we aimed to explore the biological behavior in cell motility of BMICs and understand the potential mechanisms. Methods In vitro and in vivo phage display biopanning strategies were used to isolate dodecapeptides that specifically target BMICs by selecting against primary lung cancer cells and normal brain cells. In silico analysis was used to derive specific protein targets in BMICs. Potential targets were narrowed down through analysis in patient databases and verified for their presence in BMIC through RT-PCR. Cell migration and adhesion in BMICs were analyzed using Transwell, scratch, and adhesion assays. Protein expression and cell morphology were detected by immunofluorescence. Immune blot was performed to detect the epithelial-mesenchymal related molecules and explore protein-protein interactions. Results In silico analysis of BMICs specific peptides revealed Angiomotin (Amot) as a potential target in BMICs. Amot was found to be overexpressed in BMICs compared to primary lung cancer cells. Kaplan-Meier analysis demonstrated Amot was negatively correlated with overall survival among lung adenocarcinoma patients. Knockdown of AMOT in BMICs decreased the capability of cell migration and adhesion, through the downregulation of E-Cadherin. Amot was found to maintain the E-Cadherin in BMICs through reducing ubiquitination of E-Cadherin. Furthermore, the knockdown of E-Cadherin decreased cell migration and adhesion due to the decrease in cdc42 activity. Conclusions Amot plays a role in promoting migration and adhesion in BMICs through preservation of E-Cadherin.

569 Prognostic Impact of Splicing Variants in Pediatric Brain Tumors: in Silico Analysis From High Density Microarrays

2012 ◽  
Vol 48 ◽  
pp. 174
Author(s):  
O. Pérez-Gonzalez ◽  
M. Macias-Vega ◽  
R. Cardenas-Cardos ◽  
A. Marhx-Bracho ◽  
R. Rivera-Luna
Keyword(s):  
Brain Tumors ◽  
In Silico ◽  
In Silico Analysis ◽  
Pediatric Brain Tumors ◽  
High Density ◽  
Prognostic Impact ◽  
Splicing Variants ◽  
Pediatric Brain ◽  
Silico Analysis

Downregulation of microRNA-3646 Through Direct Targeting of F-Box Protein 4 on Interleukin-17-Induced Lung Cancer Cell Migration and Invasion

2021 ◽  
Vol 11 (7) ◽  
pp. 1429-1434
Author(s):  
Ling Lin ◽  
Hongjie Zhao ◽  
Liqiang Zhai ◽  
Baoxin Xu ◽  
Ling Xiao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Lung Carcinoma ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Aberrant Expression ◽  
And Migration ◽  
E Cadherin

IL-17 participates in the initiation and growth of malignant cancers, including lung cancer. The aberrant expression of miRNA is also related to tumor growth and metastasis. Studies have confirmed that high expression of miRNA-3646 can boost breast cancer cell invasion and migration, suggesting that miRNA-3646 is a tumor-promoting factor. However, the role of miRNA-3646 in the migration and invasion of IL-17-induced lung cancer cells is unclear. In this study, qRT-PCR was used to determine the level of miRNA-3646. We found that in lung cancer cells, miRNA-3646 levels exceeded those of normal bronchial epithelial 16HBE cells (P < 0.05). The level of miRNA-3646 in NCI-H1299 cells was higher than that in A549, NCI-H446, and SK-MES-1 cells (P < 0.05). After IL-17 treatment, the number of proliferating and migrating lung carcinoma NCI-H1299 cells increased, transport of vimentin increased, and transport of E-cadherin decreased (P < 0.05). After IL-17 treatment, the number of proliferating and migrating lung carcinoma NCI-H1299 cells transfected with miRNA-3646 inhibitor decreased, transport of vimentin decreased, and transport of E-cadherin increased (P < 0.05). FBXO4 siRNA reversed the inhibition of miRNA-3646 on the proliferation and migration of IL-17-induced lung carcinoma NCI-H1299 cells and the transport of E-cadherin and vimentin. Thus, downregulation of miRNA-3646 inhibited IL-17-induced lung carcinoma cell migration and proliferation by directly targeting FBXO4.

scholarly journals p120 catenin is essential for mesenchymal cadherin–mediated regulation of cell motility and invasiveness

2006 ◽  
Vol 174 (7) ◽  
pp. 1087-1096 ◽  
Author(s):  
Masahiro Yanagisawa ◽  
Panos Z. Anastasiadis
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Tumor Progression ◽  
Cellular Phenotype ◽  
Epithelial Tumor ◽  
P120 Catenin ◽  
Rhoa Activity ◽  
Inappropriate Expression ◽  
E Cadherin

During epithelial tumor progression, the loss of E-cadherin expression and inappropriate expression of mesenchymal cadherins coincide with increased invasiveness. Reexpression experiments have established E-cadherin as an invasion suppressor. However, the mechanism by which E-cadherin suppresses invasiveness and the role of mesenchymal cadherins are poorly understood. We show that both p120 catenin and mesenchymal cadherins are required for the invasiveness of E-cadherin–deficient cells. p120 binding promotes the up-regulation of mesenchymal cadherins and the activation of Rac1, which are essential for cell migration and invasiveness. p120 also promotes invasiveness by inhibiting RhoA activity, independently of cadherin association. Furthermore, association of endogenous p120 with E-cadherin is required for E-cadherin–mediated suppression of invasiveness and is accompanied by a reduction in mesenchymal cadherin levels. The data indicate that p120 acts as a rheostat, promoting a sessile cellular phenotype when associated with E-cadherin or a motile phenotype when associated with mesenchymal cadherins.

scholarly journals Moscatilin Inhibits Lung Cancer Cell Motility and Invasion via Suppression of Endogenous Reactive Oxygen Species

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Akkarawut Kowitdamrong ◽  
Pithi Chanvorachote ◽  
Boonchoo Sritularak ◽  
Varisa Pongrakhananon
Keyword(s):  
Lung Cancer ◽  
Reactive Oxygen Species ◽  
Cell Migration ◽  
Cell Motility ◽  
Cancer Cell ◽  
Migration And Invasion ◽  
Oxygen Species ◽  
Lung Cancer Cell ◽  
Cancer Cell Motility ◽  
Endogenous Reactive Oxygen Species

Lung cancer is the leading cause of death among cancer patients worldwide, and most of them have died from metastasis. Migration and invasion are prerequisite processes associated with high metastasis potential in cancers. Moscatilin, a bibenzyl derivative isolated from the Thai orchidDendrobium pulchellum, has been shown to have anticancer effect against numerous cancer cell lines. However, little is known regarding the effect of moscatilin on cancer cell migration and invasion. The present study demonstrates that nontoxic concentrations of moscatilin were able to inhibit human nonsmall cell lung cancer H23 cell migration and invasion. The inhibitory effect of moscatilin was associated with an attenuation of endogenous reactive oxygen species (ROS), in which hydroxyl radical (OH∙) was identified as a dominant species in the suppression of filopodia formation. Western blot analysis also revealed that moscatilin downregulated activated focal adhesion kinase (phosphorylated FAK, Tyr 397) and activated ATP-dependent tyrosine kinase (phosphorylated Akt, Ser 473), whereas their parental counterparts were not detectable changed. In conclusion, our results indicate the novel molecular basis of moscalitin-inhibiting lung cancer cell motility and invasion and demonstrate a promising antimetastatic potential of such an agent for lung cancer therapy.

scholarly journals Altered expression of microRNA-223 in the plasma of patients with first-episode schizophrenia and its possible relation to neuronal migration-related genes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Zhilei Zhao ◽  
Seiichiro Jinde ◽  
Shinsuke Koike ◽  
Mariko Tada ◽  
Yoshihiro Satomura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Migration ◽  
Mirna Expression ◽  
In Silico ◽  
In Silico Analysis ◽  
Luciferase Assay ◽  
First Episode ◽  
Altered Expression ◽  
First Episode Schizophrenia ◽  
Silico Analysis

Abstract Recent studies have shown that microRNAs (miRNAs) play a role as regulators of neurodevelopment by modulating gene expression. Altered miRNA expression has been reported in various psychiatric disorders, including schizophrenia. However, the changes in the miRNA expression profile that occur during the initial stage of schizophrenia have not been fully investigated. To explore the global alterations in miRNA expression profiles that may be associated with the onset of schizophrenia, we first profiled miRNA expression in plasma from 17 patients with first-episode schizophrenia and 17 healthy controls using microarray analysis. Among the miRNAs that showed robust changes, the elevated expression of has-miR-223-3p (miR-223) was validated via quantitative reverse transcription-polymerase chain reaction (qRT-PCR) using another independent sample set of 21 schizophrenia patients and 21 controls. To identify the putative targets of miR-223, we conducted a genome-wide gene expression analysis in neuronally differentiated SK-N-SH cells with stable miR-223 overexpression and an in silico analysis. We found that the mRNA expression levels of four genes related to the cytoskeleton or cell migration were significantly downregulated in miR-223-overexpressing cells, possibly due to interactions with miR-223. The in silico analysis suggested the presence of miR-223 target sites in these four genes. Lastly, a luciferase assay confirmed that miR-223 directly interacted with the 3′ untranslated regions (UTRs) of all four genes. Our results reveal an increase in miR-223 in plasma during both the first episode and the later stage of schizophrenia, which may affect the expression of cell migration-related genes targeted by miR-223.

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