FAK-Dependent Cell Motility and Cell Elongation

Katoh, Kazuo

doi:10.3390/cells9010192

Cited by 78 publications

(59 citation statements)

References 119 publications

(179 reference statements)

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“…Upon phosphorylation, we thought that the key effectors would distribute the signal downstream to over a hundred substrates responsible for the cell migration for 12~24 h. These results are also consistent with the previous our results showing that melatonin and netrin-1 significantly induce the cell migration of UCB-MSCs within 24 h by stimulating the cytoskeletal reorganization process where the key effectors link to other molecules that are important in the cell migration process [50]. c-Src, a non-receptor tyrosine kinase, acts as an effector of integrin and/or tyrosine kinase receptor signaling, where it plays a key role in controlling membrane protrusion during cell movement [52]. c-Src, together with focal adhesion kinase (FAK), has been clearly shown to govern the formation of stress fibers and focal adhesions of discrete adhesive plaques containing numerous structural (e.g., α-actinin and vinculin) and signaling molecules (e.g., FAK, RhoA, integrins and paxillin) [53].…”

Section: Discussionsupporting

confidence: 93%

Nanospheres Loaded with Curcumin Improve the Bioactivity of Umbilical Cord Blood-Mesenchymal Stem Cells via c-Src Activation during the Skin Wound Healing Process

Kim

Choi

Park

et al. 2020

Cells

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Curcumin, a hydrophobic polyphenol derived from turmeric, has been used a food additive and as a herbal medicine for the treatment of various diseases, but the clinical application of curcumin is restricted by its poor aqueous solubility and its low permeability and bioavailability levels. In the present study, we investigate the functional role of a nanosphere loaded with curcumin (CN) in the promotion of the motility of human mesenchymal stem cells (MSCs) during the skin wound healing process. CN significantly increased the motility of umbilical cord blood (UCB)-MSCs and showed 10,000-fold greater migration efficacy than curcumin. CN stimulated the phosphorylation of c-Src and protein kinase C which are responsible for the distinctive activation of the MAPKs. Interestingly, CN significantly induced the expression levels of α-actinin-1, profilin-1 and filamentous-actin, as regulated by the phosphorylation of nuclear factor-kappa B during its promotion of cell migration. In a mouse skin excisional wound model, we found that transplantation of UCB-MSCs pre-treated with CN enhanced wound closure, granulation, and re-epithelialization at mouse skin wound sites. These results indicate that CN is a functional agent that promotes the mobilization of UCB-MSCs for cutaneous wound repair.

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Section: Discussionsupporting

confidence: 93%

Nanospheres Loaded with Curcumin Improve the Bioactivity of Umbilical Cord Blood-Mesenchymal Stem Cells via c-Src Activation during the Skin Wound Healing Process

Kim

Choi

Park

et al. 2020

Cells

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“…Protein-kinase-regulated cell migration is involved in the development of lung fibrosis [ 66 ]. Src tyrosine kinase regulates focal adhesion kinase activation and seems to cause cell elongation [ 69 ]. However, the involvements of Src tyrosine kinase in fibroblast migration and proliferation and in lung fibrosis have yet to be explored in detail.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Fibroblast Cell Polarity by Src Tyrosine Kinase

Katoh

2021

Biomedicines

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Src protein tyrosine kinases (SFKs) are a family of nonreceptor tyrosine kinases that are localized beneath the plasma membrane and are activated during cell adhesion, migration, and elongation. Due to their involvement in the activation of signal transduction cascades, SFKs have been suggested to play important roles in the determination of cell polarity during cell extension and elongation. However, the mechanism underlying Src-mediated polarity formation remains unclear. The present study was performed to investigate the mechanisms underlying Src-induced cell polarity formation and cell elongation using Src knockout fibroblasts (SYFs) together with an inhibitor of Src. Normal and Src knockout fibroblasts were also transfected with a wild-type c-Src, dominant negative c-Src, or constitutively active c-Src gene to analyze the changes in cell morphology. SYF cells cultured on a glass substrate elongated symmetrically into spindle-shaped cells, with the formation of focal adhesions at both ends of the cells. When normal fibroblasts were treated with Src Inhibitor No. 5, a selective inhibitor of Src tyrosine kinases, they elongated into symmetrical spindle-shaped cells, similar to SYF cells. These results suggest that cell polarity during extension and elongation may be regulated by SFKs and that the expression and regulation of Src are important for the formation of polarity during cell elongation.

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“…Focal adhesions are protein complexes that connect the cell cytoskeleton to the ECM and then act as scaffolds in outside-in transduction signaling [53][54][55]. In particular, the FAs-mediated intracellular pathways cooperate with receptor tyrosine kinases toward the regulation of cell shape, polarity, adhesion, migration, differentiation, survival, and proliferation [56].…”

Section: Discussionmentioning

confidence: 99%

The G Protein-Coupled Estrogen Receptor (GPER) Expression Correlates with Pro-Metastatic Pathways in ER-Negative Breast Cancer: A Bioinformatics Analysis

Talia

Francesco

Rigiracciolo

et al. 2020

Cells

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The G protein-coupled estrogen receptor (GPER, formerly known as GPR30) is a seven-transmembrane receptor that mediates estrogen signals in both normal and malignant cells. In particular, GPER has been involved in the activation of diverse signaling pathways toward transcriptional and biological responses that characterize the progression of breast cancer (BC). In this context, a correlation between GPER expression and worse clinical-pathological features of BC has been suggested, although controversial data have also been reported. In order to better assess the biological significance of GPER in the aggressive estrogen receptor (ER)-negative BC, we performed a bioinformatics analysis using the information provided by The Invasive Breast Cancer Cohort of The Cancer Genome Atlas (TCGA) project and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets. Gene expression correlation and the statistical analysis were carried out with R studio base functions and the tidyverse package. Pathway enrichment analysis was evaluated with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway on the Database for Annotation, Visualization and Integrated Discovery (DAVID) website, whereas gene set enrichment analysis (GSEA) was performed with the R package phenoTest. The survival analysis was determined with the R package survivALL. Analyzing the expression data of more than 2500 primary BC, we ascertained that GPER levels are associated with pro-migratory and metastatic genes belonging to cell adhesion molecules (CAMs), extracellular matrix (ECM)-receptor interaction, and focal adhesion (FA) signaling pathways. Thereafter, evaluating the disease-free interval (DFI) in ER-negative BC patients, we found that the subjects expressing high GPER levels exhibited a shorter DFI in respect to those exhibiting low GPER levels. Overall, our results may pave the way to further dissect the network triggered by GPER in the breast malignancies lacking ER toward a better assessment of its prognostic significance and the action elicited in mediating the aggressive features of the aforementioned BC subtype.

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FAK-Dependent Cell Motility and Cell Elongation

Cited by 78 publications

References 119 publications

Nanospheres Loaded with Curcumin Improve the Bioactivity of Umbilical Cord Blood-Mesenchymal Stem Cells via c-Src Activation during the Skin Wound Healing Process

Nanospheres Loaded with Curcumin Improve the Bioactivity of Umbilical Cord Blood-Mesenchymal Stem Cells via c-Src Activation during the Skin Wound Healing Process

Regulation of Fibroblast Cell Polarity by Src Tyrosine Kinase

The G Protein-Coupled Estrogen Receptor (GPER) Expression Correlates with Pro-Metastatic Pathways in ER-Negative Breast Cancer: A Bioinformatics Analysis

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