scholarly journals An Integrative and Modular Framework to Recapitulate Emergent Behavior in Cell Migration

2020 ◽  
Vol 8 ◽  
Author(s):  
Marina B. Cuenca ◽  
Lucía Canedo ◽  
Carolina Perez-Castro ◽  
Hernan E. Grecco
Keyword(s):  
Cell Migration ◽  
Single Cell ◽  
Cancer Progression ◽  
Collective Behavior ◽  
Cell Movement ◽  
Primary Brain Tumor ◽  
Emergent Behavior ◽  
Integrative Model ◽  
Broad Variety ◽  
Modular Framework

Cell migration has been a subject of study in a broad variety of biological systems, from morphogenetic events during development to cancer progression. In this work, we describe single-cell movement in a modular framework from which we simulate the collective behavior of glioblastoma cells, the most prevalent and malignant primary brain tumor. We used the U87 cell line, which can be grown as a monolayer or spatially closely packed and organized in 3D structures called spheroids. Our integrative model considers the most relevant mechanisms involved in cell migration: chemotaxis of attractant factor, mechanical interactions and random movement. The effect of each mechanism is integrated into the overall probability of the cells to move in a particular direction, in an automaton-like approach. Our simulations fit and reproduced the emergent behavior of the spheroids in a set of migration assays where single-cell trajectories were tracked. We also predicted the effect of migration inhibition on the colonies from simple experimental characterization of single treated cell tracks. The development of tools that allow complementing molecular knowledge in migratory cell behavior is relevant for understanding essential cellular processes, both physiological (such as organ formation, tissue regeneration among others) and pathological perspectives. Overall, this is a versatile tool that has been proven to predict individual and collective behavior in U87 cells, but that can be applied to a broad variety of scenarios.

scholarly journals HAX1 impact on collective cell migration, cell adhesion, and cell shape is linked to the regulation of actomyosin contractility

2019 ◽  
Vol 30 (25) ◽  
pp. 3024-3036 ◽  
Author(s):  
Anna Balcerak ◽  
Alicja Trebinska-Stryjewska ◽  
Maciej Wakula ◽  
Mateusz Chmielarczyk ◽  
Urszula Smietanka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Single Cell ◽  
Cancer Progression ◽  
Cancer Cell Line ◽  
Cell Junctions ◽  
Collective Cell Migration ◽  
Actomyosin Contractility ◽  
Epithelial Cell Layer ◽  
Cell Cell

HAX1 protein is involved in the regulation of apoptosis, cell motility and calcium homeostasis. Its overexpression was reported in several tumors, including breast cancer. This study demonstrates that HAX1 has an impact on collective, but not single-cell migration, thus indicating the importance of cell–cell contacts for the HAX1-mediated effect. Accordingly, it was shown that HAX1 knockdown affects cell–cell junctions, substrate adhesion, and epithelial cell layer integrity. As demonstrated here, these effects can be attributed to the modulation of actomyosin contractility through changes in RhoA and septin signaling. Additionally, it was shown that HAX1 does not influence invasive potential in the breast cancer cell line, suggesting that its role in breast cancer progression may be linked instead to collective invasion of the epithelial cells but not single-cell dissemination.

scholarly journals Nonmotile Single-Cell Migration as a Random Walk in Nonuniformity: The “Extreme Dumping Limit” for Cell-to-Cell Communications

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Grigorios P. Panotopoulos ◽  
Sebastian Aguayo ◽  
Ziyad S. Haidar
Keyword(s):  
Stochastic Process ◽  
Cell Migration ◽  
Random Walk ◽  
Single Cell ◽  
Brownian Particle ◽  
Cell Movement ◽  
Planck Equation ◽  
Equation Of Motion ◽  
Higher Moments ◽  
Cell Responses

In the present work, we model single-cell movement as a random walk in an external potential observed within the extreme dumping limit, which we define herein as the extreme nonuniform behavior observed for cell responses and cell-to-cell communications. Starting from the Newton–Langevin equation of motion, we solve the corresponding Fokker–Planck equation to compute higher moments of the displacement of the cell, and then we build certain quantities that can be measurable experimentally. We show that, each time, the dynamics depend on the external force applied, leading to predictions distinct from the standard results of a free Brownian particle. Our findings demonstrate that cell migration viewed as a stochastic process is still compatible with biological and experimental observations without the need to rely on more complicated or sophisticated models proposed previously in the literature.

scholarly journals EGF-induced nuclear translocation of SHCBP1 promotes bladder cancer progression through inhibiting RACGAP1-mediated RAC1 inactivation

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Hubin Yin ◽  
Chen Zhang ◽  
Zongjie Wei ◽  
Weiyang He ◽  
Ning Xu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Migration ◽  
Cancer Progression ◽  
Nuclear Translocation ◽  
Cell Movement ◽  
Egfr Activation ◽  
Bladder Cancer Cells ◽  
Cancer Tissues ◽  
Multiple Signaling

AbstractBladder cancer is a highly heterogeneous and aggressive malignancy with a poor prognosis. EGF/EGFR activation causes the detachment of SHC-binding protein 1 (SHCBP1) from SHC adapter protein 1 (SHC1), which subsequently translocates into the nucleus and promotes cancer development via multiple signaling pathways. However, the role of the EGF-SHCBP1 axis in bladder cancer progression remains unexplored. Herein, we report that SHCBP1 is upregulated in bladder cancer tissues and cells, with cytoplasmic or nuclear localization. Released SHCBP1 responds to EGF stimulation by translocating into the nucleus following Ser273 phosphorylation. Depletion of SHCBP1 reduces EGF-induced cell migration and invasiveness of bladder cancer cells. Mechanistically, SHCBP1 binds to RACGAP1 via its N-terminal domain of amino acids 1 ~ 428, and this interaction is enhanced following EGF treatment. Furthermore, SHCBP1 facilitates cell migration by inhibiting RACGAP-mediated GTP-RAC1 inactivation, whose activity is indispensable for cell movement. Collectively, we demonstrate that the EGF-SHCBP1-RACGAP1-RAC1 axis acts as a novel regulatory mechanism of bladder cancer progression, which offers a new clinical therapeutic strategy to combat bladder cancer.

scholarly journals A least microenvironmental uncertainty principle (LEUP) as a generative model of collective cell migration mechanisms

2018 ◽  
Author(s):  
Arnab Barua ◽  
Josue M. Nava-Sedeño ◽  
Haralampos Hatzikirou
Keyword(s):  
Cell Migration ◽  
Uncertainty Principle ◽  
Collective Behavior ◽  
Cell Movement ◽  
Generative Model ◽  
Collective Cell Migration ◽  
Proof Of Concept ◽  
Collective Migration ◽  
Vicsek Model ◽  
Special Case

AbstractCollective migration is commonly observed in groups of migrating cells, in the form of swarms or aggregates. Mechanistic models have proven very useful in understanding collective cell migration. Such models, either explicitly consider the forces involved in the interaction and movement of individuals or phenomenologically define rules which mimic the observed behavior of cells. However, mechanisms leading to collective migration are varied and specific to the type of cells involved. Additionally, the precise and complete dynamics of many important chemomechanical factors influencing cell movement, from signalling pathways to substrate sensing, are typically either too complex or largely unknown. The question is how to make quantitative/qualitative predictions of collective behavior without exact mechanistic knowledge. Here we propose the least microenvironmental uncertainty principle (LEUP) that serves as a generative model of collective migration without incorporation of full mechanistic details. Interestingly we show that the famous Vicsek model is a special case of LEUP. Finally, as a proof of concept, we apply the LEUP to quantitatively study ofthe collective behavior of spherical Serratia marcescens bacteria, where the underlying migration mechanisms remain elusive.

scholarly journals Antitumor effect of 4MU on glioblastoma cells is mediated by senescence induction and CD44, RHAMM and p-ERK modulation

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Matías Arturo Pibuel ◽  
Daniela Poodts ◽  
Mariángeles Díaz ◽  
Yamila Azul Molinari ◽  
Paula Gabriela Franco ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Migration ◽  
Cell Lines ◽  
Cancer Progression ◽  
Coumarin Derivative ◽  
Primary Brain Tumor ◽  
Membrane Receptors ◽  
Synthesis Inhibitor ◽  
Membrane Expression ◽  
Promising Alternative

AbstractThe extracellular matrix plays a key role in cancer progression. Hyaluronan, the main glycosaminoglycan of the extracellular matrix, has been related to several tumor processes. Hyaluronan acts through the interaction with cell membrane receptors as CD44 and RHAMM and triggers signaling pathways as MEK/ERK. 4-methylumbelliferone (4MU), a well-known hyaluronan synthesis inhibitor, is a promising alternative for cancer therapy. 4MU is a coumarin derivative without adverse effects that has been studied in several tumors. However, little is known about its use in glioblastoma (GBM), the most malignant primary brain tumor in adults. Glioblastoma is characterized by fast growth, migration and tissue invasiveness, and a poor median survival of the patients after treatment. Several reports linked glioblastoma progression with HA levels and even with CD44 and RHAMM expression, as well as MEK/ERK activation. Previously, we showed on a murine GBM cell line that HA enhances GBM migration, while 4MU markedly inhibits it. In this work we showed for the first time, that 4MU decreases cell migration and induces senescence in U251 and LN229 human GBM cell lines. Furthermore, we observed that HA promotes GBM cell migration on both cell lines and that such effects depend on CD44 and RHAMM, as well as MEK/ERK signaling pathway. Interestingly, we observed that the exogenous HA failed to counteract the effects of 4MU, indicating that 4MU effects are independent of HA synthesis inhibition. We found that 4MU decreases total CD44 and RHAMM membrane expression, which could explain the effect of 4MU on cell migration. Furthermore, we observed that 4MU increases the levels of RHAMM inside the cell while decreases the nucleus/cytoplasm relation of p-ERK, associated with 4MU effects on cell proliferation and senescence induction. Overall, 4MU should be considered as a promising therapeutic alternative to improve the outcome of patients with GBM.

scholarly journals A least microenvironmental uncertainty principle (LEUP) as a generative model of collective cell migration mechanisms

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Arnab Barua ◽  
Josue M. Nava-Sedeño ◽  
Michael Meyer-Hermann ◽  
Haralampos Hatzikirou
Keyword(s):  
Cell Migration ◽  
Uncertainty Principle ◽  
Collective Behavior ◽  
Statistical Physics ◽  
Cell Movement ◽  
Generative Model ◽  
Collective Cell Migration ◽  
Collective Migration ◽  
Vicsek Model ◽  
Special Case

AbstractCollective migration is commonly observed in groups of migrating cells, in the form of swarms or aggregates. Mechanistic models have proven very useful in understanding collective cell migration. Such models, either explicitly consider the forces involved in the interaction and movement of individuals or phenomenologically define rules which mimic the observed behavior of cells. However, mechanisms leading to collective migration are varied and specific to the type of cells involved. Additionally, the precise and complete dynamics of many important chemomechanical factors influencing cell movement, from signalling pathways to substrate sensing, are typically either too complex or largely unknown. The question is how to make quantitative/qualitative predictions of collective behavior without exact mechanistic knowledge. Here we propose the least microenvironmental uncertainty principle (LEUP) that may serve as a generative model of collective migration without precise incorporation of full mechanistic details. Using statistical physics tools, we show that the famous Vicsek model is a special case of LEUP. Finally, to test the biological applicability of our theory, we apply LEUP to construct a model of the collective behavior of spherical Serratia marcescens bacteria, where the underlying migration mechanisms remain elusive.

scholarly journals Regulation of Rho GTPases by RhoGDIs in Human Cancers

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1037 ◽  
Author(s):  
Cho ◽  
Kim ◽  
Baek ◽  
Kim ◽  
Lee
Keyword(s):  
Cell Migration ◽  
Cancer Progression ◽  
Anticancer Agents ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Regulatory Mechanisms ◽  
Malignant Phenotype ◽  
Cellular Processes ◽  
Human Cancers

Rho GDP dissociation inhibitors (RhoGDIs) play important roles in various cellular processes, including cell migration, adhesion, and proliferation, by regulating the functions of the Rho GTPase family. Dissociation of Rho GTPases from RhoGDIs is necessary for their spatiotemporal activation and is dynamically regulated by several mechanisms, such as phosphorylation, sumoylation, and protein interaction. The expression of RhoGDIs has changed in many human cancers and become associated with the malignant phenotype, including migration, invasion, metastasis, and resistance to anticancer agents. Here, we review how RhoGDIs control the function of Rho GTPases by regulating their spatiotemporal activity and describe the regulatory mechanisms of the dissociation of Rho GTPases from RhoGDIs. We also discuss the role of RhoGDIs in cancer progression and their potential uses for therapeutic intervention.

scholarly journals Decreased level of miR-1301 promotes colorectal cancer progression via activation of STAT3 pathway

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Fangfang Yang ◽  
Hua Wang ◽  
Bianbian Yan ◽  
Tong Li ◽  
Lulu Min ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Cancer Progression ◽  
Luciferase Assay ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Aberrant Expression ◽  
Cell Migration And Invasion ◽  
Lovo Cells ◽  
Colorectal Cancer Progression

Abstract The molecular pathogenesis of colorectal cancer (CRC) has been widely investigated in recent years. Accumulating evidence has indicated that microRNA (miRNA) dysregulation participates in the processes of driving CRC initiation and progression. Aberrant expression of miR-1301 has been found in various tumor types. However, its role in CRC remains to be elucidated. In the present study, we identified miR-1301 was enriched in normal colorectal tissues and significantly down-regulated in CRC. Decreased level of miR-1301 strongly correlated with aggressive pathological characteristics, including advanced stage and metastasis. Bioinformatics and dual luciferase assay demonstrated that STAT3 is a direct target of miR-1301. Gain and loss-of-function assays showed that miR-1301 had no effect on cell proliferation. Overexpression of miR-1301 suppressed cell migration and invasion capacity of pSTA3-positive LoVo cells, but not pSTAT3-negative SW480 cells, while inhibition of miR-1301 consistently promoted cell migration and invasion in both cell lines. Additionally, miR-1301 inhibition restored the suppressed migration and invasion of STAT3- knockdown LoVo cells. MiR-1301 functioned as a tumor suppressor to modulate the IL6/STAT3 signaling pathway. In summary, this study highlights the significant role of miR- 1301/STAT3 axis in CRC metastasis.

scholarly journals Chemotactic Responses of Jurkat Cells in Microfluidic Flow-Free Gradient Chambers

Micromachines ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 384 ◽  
Author(s):  
Utku M. Sonmez ◽  
Adam Wood ◽  
Kyle Justus ◽  
Weijian Jiang ◽  
Fatima Syed-Picard ◽  
...  
Keyword(s):  
Immune Response ◽  
Cancer Progression ◽  
Soft Lithography ◽  
Cell Movement ◽  
Population Level ◽  
Jurkat Cells ◽  
Dependent Manner ◽  
Diverse Range ◽  
Microfluidic Flow ◽  
Cell Motion

Gradients of soluble molecules coordinate cellular communication in a diverse range of multicellular systems. Chemokine-driven chemotaxis is a key orchestrator of cell movement during organ development, immune response and cancer progression. Chemotaxis assays capable of examining cell responses to different chemokines in the context of various extracellular matrices will be crucial to characterize directed cell motion in conditions which mimic whole tissue conditions. Here, a microfluidic device which can generate different chemokine patterns in flow-free gradient chambers while controlling surface extracellular matrix (ECM) to study chemotaxis either at the population level or at the single cell level with high resolution imaging is presented. The device is produced by combining additive manufacturing (AM) and soft lithography. Generation of concentration gradients in the device were simulated and experimentally validated. Then, stable gradients were applied to modulate chemotaxis and chemokinetic response of Jurkat cells as a model for T lymphocyte motility. Live imaging of the gradient chambers allowed to track and quantify Jurkat cell migration patterns. Using this system, it has been found that the strength of the chemotactic response of Jurkat cells to CXCL12 gradient was reduced by increasing surface fibronectin in a dose-dependent manner. The chemotaxis of the Jurkat cells was also found to be governed not only by the CXCL12 gradient but also by the average CXCL12 concentration. Distinct migratory behaviors in response to chemokine gradients in different contexts may be physiologically relevant for shaping the host immune response and may serve to optimize the targeting and accumulation of immune cells to the inflammation site. Our approach demonstrates the feasibility of using a flow-free gradient chamber for evaluating cross-regulation of cell motility by multiple factors in different biologic processes.

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