• Journal of Integrative Natural Science
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• v.4 no.4
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• pp.266-272
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• 2011

Focal adhesion kinase (FAK) is a potential target for the treatment of primary cancers as well as prevention of tumor metastasis. To understand the structural and chemical features of FAK inhibitors, we report comparative molecular field analysis (CoMFA) for the series of 7H-pyrrolo(2,3-d)pyrimidines. The CoMFA models showed good correlation between the actual and predicted values for training set molecules. Our results indicated the ligand-based alignment has produced better statistical results for CoMFA ($q^2$ = 0.505, $r^2$ = 0.950). Both models were validated using test set compounds, and gave good predictive values of 0.537. The statistical parameters from the generated 3D-QSAR models were indicated that the data are well fitted and have high predictive ability. The contour map from 3D-QSAR models explains nicely the structure-activity relationships of FAK inhibitors and our results would give proper guidelines to further enhance the activity of novel inhibitors.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.166.1-166.1
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• 2003

Autotaxin (ATX) is a 125-kDa glycoprotein and a strong motogen that can increase invasiveness and angiogenesis, originally isolated from the conditioned medium of human melanoma A2058 cells. And it is a strong. Recently, we suggested that ATX promotes motility via G protein-coupled PI3K$\gamma$, and Cdc42/Racl are essential for ATX-induced tumor cell motility in A2058 melanoma cells. In the present study, we found that activation of p21-activated kinase1 (PAK1) was required for ATX-induced cell motility. (omitted)

• Proceedings of the Microbiological Society of Korea Conference
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• 2004.05a
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• pp.141-146
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• 2004

SPIN90 was identified to farm molecular complex with $\betaPIX$, WASP and Nck. This complex shows that SPIN90 interacts with Nck in a manner dependent upon cell adhesion to extracellular matrix, but $SPIN90{\cdot}{\beta}PIX{\cdot}WASP$ complex was stable even in suspended cells. This suggests that SPIN90 serves as an adaptor molecule to recruit other proteins to Nck at focal adhesions. SPIN90 was phosphorylated by ERK1, which was, itself, activated by cell adhesion and platelet-derived growth factor. Such phosphorylation of SPIN90 likely promotes the interaction of the $SPIN90{\cdot}{\beta}PIX{\cdot}WASP$ complex and Nck. It thus appears that the interaction of the $SPIN90{\cdot}{\beta}PIX{\cdot}WASP$ complex with Nck is crucial for stable cell adhesion and can be dynamically modulated by SPIN90 phosphorylation that is dependent on cell adhesion and ERX activation. SPIN90 directly binds syndapin I, syndapin isoform II-1 and II-s via its PRD region in vitro, in vivo and also associates with endocytosis core components such as clathrin and dynamin. In neuron and fibroblast, SPIN90 colocalizes with syndapins as puntate form, consistent with a role for SPIN90 in clathrin-mediated endocytosis pathway. Overexpression of SPIN90 N-term inhibits receptor-mediated endocytosis. Interestingly, SPIN90 PRD, binding interface of syndapin, significantly blocks internalization of transferrin, demonstrating SPIN90 involvement in endocytosis in vivo by interacting syndapin. Depletion of endogenous SPIN90 by introducing $\alpha-SPIN90$ also blocks receptor-mediated endocytosis. Actin polymerization could generate farce facilitating the pinch-out event in endocytosis, detach newly formed endocytic vesicle from the plasma membrane or push out them via the cytosol on actin tails. Here we found that SPIN90 localizes to high actin turn over cortical area, actin-membrane interface and membrane ruffle in PDGF treated cells. Overexpression of SPIN90 has an effect on cortical actin rearrangement as filopodia induction and it is mediated by the Arp2/3 complex at cell periphery. Consistent with a role in actin organization, CFP-SPIN90 present in actin comet tail generated by PIP5 $kinase\gamma$ overexpression. Therefore this study suggests that SPIN90 is functional linker between endocytosis and actin cytoskeleton.

• Clinical and Experimental Reproductive Medicine
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• v.33 no.2
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• pp.115-123
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• 2006

Objective: To investigate new signal transduction cascade through integrin, FAK and ERK in the suppressed cell proliferation by GnRH-I and -II. Method: Human endometrial cancer cells (HEC1A) were cultured under the following condition: DMEM/F12 (10% FBS). GnRH-I and -II were treated time (0, 5, 10, 15, 20, 30 min; 100 nM) and dose (10 nM or 100 nM; 20 min) dependent manner according to experimental purposes. Cell proliferation was measured using [$^3H$] thymidine incorporation assay. Immunoblotting was utilized to detect proteins. Results: GnRH-I and -II inhibited proliferation of HEC1A cells and induced expression of integrin ${\beta}3$. Phosphorylation of FAK and ERK were induced by GnRH-I and -II. Conclusion: GnRH inhibited cell proliferation via the expression of integrin and FAK, ERK phosphorylation.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3741-3745
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• 2012

Background: Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the most common form of liver cancer. However, while it is associated frequently with hepatitis C virus (HCV) there is only an elementary understanding of its molecular pathogenesis. Methods: To gain insight into the molecular mechanisms of HCV-induced hepatocarcinogenesis, we performed microarray analysis on 75 surgical liver samples from 48 HCV-infected patients. Results: There were 395 differentially expressed geness between cirrhotic samples and HCC samples. Of these, 125 genes were up-regulated and 270 genes were down-regulated. We performed pathway enrichment analysis and screened as described previously. Conclusions: The differentially expressed genes might be involved in hepatocarcinogenesis through upregulating the pathways of ECM-receptor interaction, focal adhesion, cell adhesion molecules and other cancer-related pathways, and downregulating the pathways of "complement and coagulation cascades". We hope our results could aid in seeking of therapeutic targets for HCV-induced hepatocellular carcinoma.

• IMMUNE NETWORK
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• v.11 no.6
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• pp.390-398
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• 2011

Background: Epstein Barr virus (EBV) infected B cells are transformed into lymphoblastoid cell lines. Some researchers suggested some a few similarities between this process and carcinogenesis. We observed the expression of CD80 and CD86, co-stimulatory molecules on EBV-transformed B cells and changes of CD54 expression after stimulation of CD80 and CD86. Methods: CD80 and CD86 were stimulated using anti-CD80 and anti-CD86 monoclonal antibodies. To assess apoptosis and surface protein expression, flow cytometric analysis was performed. Intracellular signal molecules were evaluated by RT-PCR and immunoblot. Morphology and localization of proteins were examined using inverted or confocal microscope. Results: Cross-linking of CD80 and CD86 induced apoptosis and interfered with proliferation of EBV-transformed B cells, and dispersion of clumped cells. We also examined that their stimulation induced ROS accumulation and reduced CD54 expression. Interestingly, we observed that CD80 and CD86 diminished the expression of CD54 in different methods. Both CD80 and CD86 downregulated activation of focal adhesion kinase. CD80 stimulus inhibited CD54 expression through mainly RhoA inactivation, while CD86 down-regulated Ras and JNK phosphorylation. Conclusion: These results suggest that co-stimulatory CD80 and CD86 molecules, expressed EBV-transformed B cells, may play a role in apoptosis and cell adhesion.

• Journal of Animal Science and Technology
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• v.62 no.6
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• pp.765-776
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• 2020

The retinal degenerative disease, progressive retinal atrophy (PRA) is a major reason of vision impairment in canine population. Canine PRA signifies an inherently dissimilar category of retinal dystrophies which has solid resemblances to human retinis pigmentosa. Even though much is known about the biology of PRA, the knowledge about the intricate connection among genetic loci, genes and pathways associated to this disease in dogs are still remain unknown. Therefore, we have performed a genome wide association study (GWAS) to identify susceptibility single nucleotide polymorphisms (SNPs) of PRA. The GWAS was performed using a case-control based association analysis method on PRA dataset of 129 dogs and 135,553 markers. Further, the gene-set and pathway analysis were conducted in this study. A total of 1,114 markers associations with PRA trait at p < 0.01 were extracted and mapped to 640 unique genes, and then selected significant (p < 0.05) enriched 35 gene ontology (GO) terms and 5 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways contain these genes. In particular, apoptosis process, homophilic cell adhesion, calcium ion binding, and endoplasmic reticulum GO terms as well as pathways related to focal adhesion, cyclic guanosine monophosphate)-protein kinase G signaling, and axon guidance were more likely associated to the PRA disease in dogs. These data could provide new insight for further research on identification of potential genes and causative pathways for PRA in dogs.

• Journal of Ginseng Research
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• v.47 no.4
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• pp.493-505
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• 2023

In recent years, an increasing number of reports have explored the wound healing mechanism of these two traditional Chinese herbal medicines- Panax ginseng and Panax notoginseng, but there is no systematic research on the related core functions and different mechanisms in the treatment of wound healing up to now. Based on network pharmacology and meta-analysis, the present work aimed to comprehensively review the commonality and diversity of P. ginseng and P. notoginseng in wound healing. In this study, a wound healing-related "ingredients-targets" network of two herbs was constructed. Thereafter, meta-analysis of the multiple target lists by Metascape showed that these two medicines significantly regulated blood vessel development, responses to cytokines and growth factors and oxygen levels, cell death, cell proliferation and differentiation, and cell adhesion. To better understand the discrepancy between these two herbs, it was found that common signaling pathways including Rap1, PI3K/AKT, MAPK, HIF-1 and Focal adhesion regulated the functions listed above. In parallel, the different pathways including renin-angiotensin system, RNA transport and circadian rhythm, autophagy, and the different metabolic pathways may also explained the discrepancies in the regulation of the above-mentioned functions, consistent with the Traditional Chinese Medicine theory about the effects of P. ginseng and P. notoginseng.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.21 no.3
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• pp.36-51
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• 2008

Objective : This study investigated the effects of PR(Pinelliae Rhizoma) on gene expression of lung tissue resected from asthma induced mice using intra-nasal instillation. Methods : Gene expression levels were measured using a microarray technique, and a functional analysis on these genes was conducted. Results : A total of 3270 genes were up-regulated or down-regulated, 860 genes which were lowered by induction of asthma were restored to those of naive animals, Furthermore hand, 1235 genes were lowered to normal levels, which were elevated by induction of asthma. Most of changed genes were involved in signalling pathways. Genes in which expression levels were restored by oral administration of PR were involved in MAPK pathway, focal adhesion, and regulation of actin cytoskeleton etc. Genes of which expression levels were lowered by oral administration of PR were involved in rhodopsin-like receptor activity, zinc ion binding and ATP binding. These genes were also involved in neuroactive ligand receptor interaction, the JAK-STAT signaling pathway and also the T-cell receptor signaling pathway. Conclusion : These results demonstrate the strong possibility that the mechanisms of PR on asthma are involved in neuroactive ligand receptor interaction pathway or related molecules.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.22 no.3
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• pp.47-62
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• 2009

Glenditsia spina (GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. For these reasons, GS has been widely used as dermatologic agent clinically. In this study, the specific pathways of anti-proliferative effect of GS on human derived melanoma cells were identified. The molecular profile was measured using microarray technique to identify up- or down-regulated genes in SK-MEL-2 cell line. Pathway analysis was done by listing percentage of pathway involvement, and the represented pathways were obtained from KEGG. The transcription factor binding sequences were obtained by Transfac database. By the promoter analysis, up-regulated genes by GS were mainly associated with MAPK, Regulation of actin cytoskeleton, Wnt, Focal adhesion and Long term potentiation pathway. Down-regulated genes by GS were mainly associated with MAPK and Antigen processing and presentation pathway. And some of the transcription factors like Sp1 and NF-Y in up-regulated genes and Oct-1 in down-regulated genes by GS also identified.