scholarly journals Actinin-4, a Novel Actin-bundling Protein Associated with Cell Motility and Cancer Invasion

1998 ◽  
Vol 140 (6) ◽  
pp. 1383-1393 ◽  
Author(s):  
Kazufumi Honda ◽  
Tesshi Yamada ◽  
Ritsuko Endo ◽  
Yoshinori Ino ◽  
Masahiro Gotoh ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Cell Motility ◽  
Cell Movement ◽  
Metastatic Potential ◽  
Cancer Invasion ◽  
Cytoplasmic Localization ◽  
Cellular Motility ◽  
Phosphatidylinositol 3 Kinase ◽  
Antigenic Protein ◽  
Histological Phenotype

Regulation of the actin cytoskeleton may play a crucial role in cell motility and cancer invasion. We have produced a monoclonal antibody (NCC- Lu-632, IgM, k) reactive with an antigenic protein that is upregulated upon enhanced cell movement. The cDNA for the antigen molecule was found to encode a novel isoform of nonmuscle α-actinin. This isoform (designated actinin-4) was concentrated in the cytoplasm where cells were sharply extended and in cells migrating and located at the edge of cell clusters, but was absent from focal adhesion plaques or adherens junctions, where the classic isoform (actinin-1) was concentrated. Actinin-4 shifted steadily from the cytoplasm to the nucleus upon inhibition of phosphatidylinositol 3 kinase or actin depolymerization. The cytoplasmic localization of actinin-4 was closely associated with an infiltrative histological phenotype and correlated significantly with a poorer prognosis in 61 cases of breast cancer. These findings suggest that cytoplasmic actinin-4 regulates the actin cytoskeleton and increases cellular motility and that its inactivation by transfer to the nucleus abolishes the metastatic potential of human cancers.

Aggregation of Burkitt Lymphoma Cells in Stationary Culture: Experimental and Theoretical Analysis

1972 ◽  
Vol 10 (3) ◽  
pp. 749-758
Author(s):  
E. MAYHEW ◽  
L. E. BLUMENSON
Keyword(s):  
Computer Simulation ◽  
Cell Motility ◽  
Burkitt Lymphoma ◽  
Cell Movement ◽  
Experimental System ◽  
Cell Aggregation ◽  
Cellular Motility ◽  
Final Size ◽  
Lymphoma Cells ◽  
Aggregation Behaviour

Cellular motility plays an important role in natural aggregative phenomena but previously has been difficult to quantitate. We here describe a general method which can be used to determine the importance of cell motility in cell aggregation behaviour. When actively moving Burkitt lymphoma cells cultured in microtest plate wells come into contact they adhere to one another forming an aggregate. The aggregate increases in size when more cells come in contact with it. The final size and number of aggregates per well was found to be dependent on the number of cells added per well. With increasing cell numbers added per well the number of aggregates formed increased until it reached a peak of 47-57 aggregates per well 20 h after the addition of 180-710 cells per well. At higher cell concentrations the number of aggregates formed decreased. The system was analysed theoretically by programming a computer to simulate the experimental system. This simulation showed it was probable that the experimental results obtained were due to (a) random dropping of the cells at zero time and (b) the adhesion of the cells when they made contact and (c) unrestricted random movement of cells in the well when they reached the well surface. The computer simulation is such that given the experimentally determined cell concentration per well and rate of cell movement we can predict the number of aggregates formed for different probabilities that the adhesions formed after the cells come in contact are permanent. This experimental approach along with the computer simulation can be used to quantitate the role of cell motility and permanence of contact in cell aggregation.

scholarly journals Neuropeptide Y/Y5 Receptor Pathway Stimulates Neuroblastoma Cell Motility Through RhoA Activation

2021 ◽  
Vol 8 ◽  
Author(s):  
Nouran Abualsaud ◽  
Lindsay Caprio ◽  
Susana Galli ◽  
Ewa Krawczyk ◽  
Lamia Alamri ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Cell Motility ◽  
Neuroblastoma Cell ◽  
Cell Movement ◽  
Cellular Motility ◽  
Rhoa Activity ◽  
Rhoa Activation ◽  
Cytoskeleton Remodeling ◽  
Cancer Dissemination ◽  
Migratory Cells

Neuropeptide Y (NPY) has been implicated in the regulation of cellular motility under various physiological and pathological conditions, including cancer dissemination. Yet, the exact signaling pathways leading to these effects remain unknown. In a pediatric malignancy, neuroblastoma (NB), high NPY release from tumor tissue associates with metastatic disease. Here, we have shown that NPY stimulates NB cell motility and invasiveness and acts as a chemotactic factor for NB cells. We have also identified the Y5 receptor (Y5R) as the main NPY receptor mediating these actions. In NB tissues and cell cultures, Y5R is highly expressed in migratory cells and accumulates in regions of high RhoA activity and dynamic cytoskeleton remodeling. Y5R stimulation activates RhoA and results in Y5R/RhoA-GTP interactions, as shown by pull-down and proximity ligation assays, respectively. This is the first demonstration of the role for the NPY/Y5R axis in RhoA activation and the subsequent cytoskeleton remodeling facilitating cell movement. These findings implicate Y5R as a target in anti-metastatic therapies for NB and other cancers expressing this receptor.

scholarly journals 2D or 3D? How in vitro cell motility is conserved across dimensions, and predicts in vivo invasion

2019 ◽  
Author(s):  
Sualyneth Galarza ◽  
Hyuna Kim ◽  
Naciye Atay ◽  
Shelly R Peyton ◽  
Jennifer M Munson
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Cell Movement ◽  
Complex Model ◽  
Model Systems ◽  
Cellular Motility ◽  
Statistical Tool ◽  
3D Environments

AbstractCell motility is a critical aspect of wound healing, the immune response, and is deregulated in cancer. Current limitations in imaging tools make it difficult to study cell migration in vivo. To overcome this, and to identify drivers from the microenvironment that regulate cell migration, bioengineers have developed 2D and 3D tissue model systems in which to study cell motility in vitro, with the aim of mimicking the environments in which cells move in vivo. However, there has been no systematic study to explicitly relate and compare cell motility measurements between these geometries/systems. Here, we provide such analysis on our own data, as well as across data in existing literature to understand whether, and which, in vitro models are predictive of in vivo cell motility. To our surprise, many metrics of cell movement on 2D surfaces significantly and positively correlate with cell migration in 3D environments, and cell invasion in 3D is negatively correlated with glioblastoma invasion in vivo. Finally, to best compare across complex model systems, in vivo data, and data from different labs, we suggest that groups report an effect size, a statistical tool that is most translatable across experiments and labs, when conducting experiments that affect cellular motility.

scholarly journals Modulation of Cellular Migration and Survival by c-Myc through the Downregulation of Urokinase (uPA) and uPA Receptor

2010 ◽  
Vol 30 (7) ◽  
pp. 1838-1851 ◽  
Author(s):  
Daniela Alfano ◽  
Giuseppina Votta ◽  
Almut Schulze ◽  
Julian Downward ◽  
Mario Caputi ◽  
...  
Keyword(s):  
Cell Motility ◽  
Cellular Transformation ◽  
Tumor Formation ◽  
Cellular Migration ◽  
Epithelial Cell Line ◽  
Cellular Motility ◽  
Upa Receptor ◽  
Upar Expression ◽  
Repressive Effect ◽  
Cell Invasiveness

ABSTRACT It has been proposed that c-Myc proapoptotic activity accounts for most of its restraint of tumor formation. We established a telomerase-immortalized human epithelial cell line expressing an activatable c-Myc protein. We found that c-Myc activation induces, in addition to increased sensitivity to apoptosis, reductions in cell motility and invasiveness. Transcriptome analysis revealed that urokinase (uPA) and uPA receptor (uPAR) were strongly downregulated by c-Myc. Evidence is provided that the repression of uPA and uPAR may account for most of the antimigratory and proapoptotic activities of c-Myc. c-Myc is known to cooperate with Ras in cellular transformation. We therefore investigated if this cooperation could converge in the control of uPA/uPAR expression. We found that Ras is able to block the effects of c-Myc activation on apoptosis and cellular motility but not on cell invasiveness. Accordingly, the activation of c-Myc in the context of Ras expression had only minor influence on uPAR expression but still had a profound repressive effect on uPA expression. Thus, the differential regulation of uPA and uPAR by c-Myc and Ras correlates with the effects of these two oncoproteins on cell motility, invasiveness, and survival. In conclusion, we have discovered a novel link between c-Myc and uPA/uPAR. We propose that reductions of cell motility and invasiveness could contribute to the inhibition of tumorigenesis by c-Myc and that the regulation of uPA and uPAR expression may be a component of the ability of c-Myc to reduce motility and invasiveness.

scholarly journals Activation of the osmo-sensitive chloride conductance involves P21rho and is accompanied by a transient reorganization of the F-actin cytoskeleton.

1996 ◽  
Vol 7 (9) ◽  
pp. 1419-1427 ◽  
Author(s):  
B C Tilly ◽  
M J Edixhoven ◽  
L G Tertoolen ◽  
N Morii ◽  
Y Saitoh ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Chloride Channels ◽  
Kinase Activity ◽  
Specific Inhibitor ◽  
Dominant Negative ◽  
Cell Swelling ◽  
Phosphatidylinositol 3 Kinase ◽  
C3 Exoenzyme ◽  
Original Cell ◽  
Adp Ribosyltransferase

Hypo-osmotic stimulation of human Intestine 407 cells rapidly activated compensatory CL- and K+ conductances that limited excessive cell swelling and, finally, restored the original cell volume. Osmotic cell swelling was accompanied by a rapid and transient reorganization of the F-actin cytoskeleton, affecting both stress fibers as well as apical ruffles. In addition, an increase in total cellular F-actin was observed. Pretreatment of the cells with recombinant Clostridium botulinum C3 exoenzyme, but not with mutant enzyme (C3-E173Q) devoid of ADP-ribosyltransferase activity, greatly reduced the activation of the osmo-sensitive anion efflux, suggesting a role for the ras-related GTPase p21rho. In contrast, introducing dominant negative N17-p21rac into the cells did not affect the volume-sensitive efflux. Cell swelling-induced reorganization of F-actin coincided with a transient, C3 exoenzyme-sensitive tyrosine phosphorylation of p125 focal adhesion kinase (p125FAK) as well as with an increase in phosphatidylinositol-3-kinase (PtdIns-3-kinase) activity. Pretreatment of the cells with wortmannin, a specific inhibitor of PtdIns-3-kinase, largely inhibited the volume-sensitive ion efflux. Taken together, our results indicate the involvement of a p21rho signaling cascade and actin filaments in the activation of volume-sensitive chloride channels.

scholarly journals The Heterochronic microRNA let-7 Inhibits Cell Motility by Regulating the Genes in the Actin Cytoskeleton Pathway in Breast Cancer

2013 ◽  
Vol 11 (3) ◽  
pp. 240-250 ◽  
Author(s):  
Xiaowen Hu ◽  
Jinyi Guo ◽  
Lan Zheng ◽  
Chunsheng Li ◽  
Tim M. Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Actin Cytoskeleton ◽  
Cell Motility

scholarly journals Joining forces: crosstalk between biochemical signalling and physical forces orchestrates cellular polarity and dynamics

2018 ◽  
Vol 373 (1747) ◽  
pp. 20170145 ◽  
Author(s):  
Suvrajit Saha ◽  
Tamas L. Nagy ◽  
Orion D. Weiner
Keyword(s):  
Cell Biology ◽  
Cell Movement ◽  
Special Focus ◽  
Cellular Motility ◽  
Cellular Polarity ◽  
Self Organized ◽  
Cytoskeletal Dynamics ◽  
Physical Forces ◽  
Cytoskeletal Rearrangements

Dynamic processes like cell migration and morphogenesis emerge from the self-organized interaction between signalling and cytoskeletal rearrangements. How are these molecular to sub-cellular scale processes integrated to enable cell-wide responses? A growing body of recent studies suggest that forces generated by cytoskeletal dynamics and motor activity at the cellular or tissue scale can organize processes ranging from cell movement, polarity and division to the coordination of responses across fields of cells. To do so, forces not only act mechanically but also engage with biochemical signalling. Here, we review recent advances in our understanding of this dynamic crosstalk between biochemical signalling, self-organized cortical actomyosin dynamics and physical forces with a special focus on the role of membrane tension in integrating cellular motility. This article is part of the theme issue ‘Self-organization in cell biology’.

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