scholarly journals Fine Tuning Cell Migration by a Disintegrin and Metalloproteinases

2017 ◽  
Vol 2017 ◽  
pp. 1-22 ◽  
Author(s):  
D. Dreymueller ◽  
K. Theodorou ◽  
M. Donners ◽  
A. Ludwig
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Immune Cell ◽  
Tissue Homeostasis ◽  
Fine Tuning ◽  
Tissue Cell ◽  
Cancer Cell Migration ◽  
Physiological Processes ◽  
Cell Tissue ◽  
And Migration

Cell migration is an instrumental process involved in organ development, tissue homeostasis, and various physiological processes and also in numerous pathologies. Both basic cell migration and migration towards chemotactic stimulus consist of changes in cell polarity and cytoskeletal rearrangement, cell detachment from, invasion through, and reattachment to their neighboring cells, and numerous interactions with the extracellular matrix. The different steps of immune cell, tissue cell, or cancer cell migration are tightly coordinated in time and place by growth factors, cytokines/chemokines, adhesion molecules, and receptors for these ligands. This review describes how a disintegrin and metalloproteinases interfere with several steps of cell migration, either by proteolytic cleavage of such molecules or by functions independent of proteolytic activity.

scholarly journals WDR5 modulates cell motility and morphology and controls nuclear changes induced by a 3D environment

2018 ◽  
Vol 115 (34) ◽  
pp. 8581-8586 ◽  
Author(s):  
Pengbo Wang ◽  
Marcel Dreger ◽  
Elena Madrazo ◽  
Craig J. Williams ◽  
Rafael Samaniego ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Underlying Mechanism ◽  
H3k4 Methylation ◽  
Nuclear Mechanics ◽  
3D Environment ◽  
3D Environments ◽  
And Migration

Cell migration through extracellular matrices requires nuclear deformation, which depends on nuclear stiffness. In turn, chromatin structure contributes to nuclear stiffness, but the mechanosensing pathways regulating chromatin during cell migration remain unclear. Here, we demonstrate that WD repeat domain 5 (WDR5), an essential component of H3K4 methyltransferase complexes, regulates cell polarity, nuclear deformability, and migration of lymphocytes in vitro and in vivo, independent of transcriptional activity, suggesting nongenomic functions for WDR5. Similarly, depletion of RbBP5 (another H3K4 methyltransferase subunit) promotes similar defects. We reveal that a 3D environment increases the H3K4 methylation dependent on WDR5 and results in a globally less compacted chromatin conformation. Further, using atomic force microscopy, nuclear particle tracking, and nuclear swelling experiments, we detect changes in nuclear mechanics that accompany the epigenetic changes induced in 3D conditions. Indeed, nuclei from cells in 3D environments were softer, and thereby more deformable, compared with cells in suspension or cultured in 2D conditions, again dependent on WDR5. Dissecting the underlying mechanism, we determined that actomyosin contractility, through the phosphorylation of myosin by MLCK (myosin light chain kinase), controls the interaction of WDR5 with other components of the methyltransferase complex, which in turn up-regulates H3K4 methylation activation in 3D conditions. Taken together, our findings reveal a nongenomic function for WDR5 in regulating H3K4 methylation induced by 3D environments, physical properties of the nucleus, cell polarity, and cell migratory capacity.

scholarly journals P-cadherin promotes collective cell migration via a Cdc42-mediated increase in mechanical forces

2016 ◽  
Vol 212 (2) ◽  
pp. 199-217 ◽  
Author(s):  
Cédric Plutoni ◽  
Elsa Bazellieres ◽  
Maïlys Le Borgne-Rochet ◽  
Franck Comunale ◽  
Agusti Brugues ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Cell Biology ◽  
Cell Polarization ◽  
Collective Cell Migration ◽  
Mechanical Forces ◽  
Tumor Aggressiveness ◽  
And Migration ◽  
Cell Cell

Collective cell migration (CCM) is essential for organism development, wound healing, and metastatic transition, the primary cause of cancer-related death, and it involves cell–cell adhesion molecules of the cadherin family. Increased P-cadherin expression levels are correlated with tumor aggressiveness in carcinoma and aggressive sarcoma; however, how P-cadherin promotes tumor malignancy remains unknown. Here, using integrated cell biology and biophysical approaches, we determined that P-cadherin specifically induces polarization and CCM through an increase in the strength and anisotropy of mechanical forces. We show that this mechanical regulation is mediated by the P-cadherin/β-PIX/Cdc42 axis; P-cadherin specifically activates Cdc42 through β-PIX, which is specifically recruited at cell–cell contacts upon CCM. This mechanism of cell polarization and migration is absent in cells expressing E- or R-cadherin. Thus, we identify a specific role of P-cadherin through β-PIX–mediated Cdc42 activation in the regulation of cell polarity and force anisotropy that drives CCM.

Cell Polarity and Migration: Emerging Role for the Endosomal Sorting Machinery

Physiology ◽  
2011 ◽  
Vol 26 (3) ◽  
pp. 171-180 ◽  
Author(s):  
Viola Hélène Lobert ◽  
Harald Stenmark
Keyword(s):  
Cell Migration ◽  
Cell Division ◽  
Cell Polarity ◽  
Tumor Suppressors ◽  
Potential Role ◽  
Endosomal Sorting ◽  
Escrt Machinery ◽  
Viral Budding ◽  
And Migration

The endosomal sorting complex required for transport (ESCRT) machinery has been implicated in the regulation of endosomal sorting, cell division, viral budding, autophagy, and cell signaling. Here, we review recent evidence that implicates ESCRTs in cell polarity and cell migration, and discuss the potential role of ESCRTs as tumor suppressors.

scholarly journals LncRNA BANCR Facilitates Melanoma Cells Growth, Migration and Invasion by Inhibiting miR-206 and miR-571 to Induce G6PD Expression

2020 ◽  
Author(s):  
Yuye Yang ◽  
Huixin Yang ◽  
Zihan Yi ◽  
Lijuan Yang ◽  
Yueli Ni ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Nude Mice ◽  
Melanoma Cells ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Mice Model ◽  
Nude Mice Model ◽  
And Migration

Abstract Background Here, we evaluated the roles of LncRNA BANCR in facilitating melanoma cells growth, migration, invasion. Moreover, we examined the molecular mechanisms of BANCR in promoting melanoma development.Methods Here, we measured BANCR expression by quantitative PCR. By transwell assay, we detected the cancer cell migration and invasion. The melanoma growth and migration induced by BANCR was detected by colony formation assay and in xenograft nude mice model. By Western blotting and luciferase assay, we evaluated the molecular mechanism of BANCR in inhibiting miR-206 and miR-571 to induce G6PD expression. Results We found BANCR was overexpressed in melanoma cells and tissues. In addition, we showed that BANCR promoted melanoma cells growth in vitro and in vivo. Moreover, BANCR promotes cancer cell migration and invasion in vitro, and induced melanoma metastasis in nude mice model. The migration and invasion induced by BANCR in melanoma cells were involved in upregulation of matrix metalloproteinases (MMPs) MMP2 and MMP9. Mechanismly, we indicated BANCR promoted melanoma cell growth and migration by suppressing miR-206 and miR-571 expression to activate glucose metabolism pathway and induce G6PD expression. Furthermore, miR-206 and miR-571 inhibited G6PD expression by directly binding the 3’UTR of G6PD. We also showed miR-206 and miR-571 inhibited the proliferation of melanoma cells.Conclusion Our findings indicated that BANCR contributed to melanoma development, which might provide novel insights into the function of lncRNA-driven carcinogenesis in melanoma.

scholarly journals Human Aquaporin-5 Facilitates Hydrogen Peroxide Permeation Affecting Adaption to Oxidative Stress and Cancer Cell Migration

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 932 ◽  
Author(s):  
Claudia Rodrigues ◽  
Catarina Pimpão ◽  
Andreia F. Mósca ◽  
Ana S. Coxixo ◽  
Duarte Lopes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Migration ◽  
Cell Growth ◽  
Cancer Cell ◽  
Fine Tuning ◽  
Human Pancreatic Cancer ◽  
Cancer Cell Migration ◽  
Influx Rate ◽  
Water Permeation ◽  
Pancreatic Cancer Cells

Reactive oxygen species (ROS), including H2O2, contribute to oxidative stress and may cause cancer initiation and progression. However, at low concentrations, H2O2 can regulate signaling pathways modulating cell growth, differentiation, and migration. A few mammalian aquaporins (AQPs) facilitate H2O2 diffusion across membranes and participate in tumorigenesis. AQP3 and AQP5 are strongly expressed in cancer tissues and AQP3-mediated H2O2 transport has been related to breast cancer cell migration, but studies with human AQP5 are lacking. Here, we report that, in addition to its established water permeation capacity, human AQP5 facilitates transmembrane H2O2 diffusion and modulates cell growth of AQP5-transformed yeast cells in response to oxidative stress. Mutagenesis studies revealed that residue His173 located in the selective filter is crucial for AQP5 permeability, and interactions with phosphorylated Ser183 may regulate permeation through pore blockage. Moreover, in human pancreatic cancer cells, the measured AQP5-mediated H2O2 influx rate indicates the presence of a highly efficient peroxiporin activity. Cell migration was similarly suppressed by AQP3 or AQP5 gene silencing and could be recovered by external oxidative stimuli. Altogether, these results unveiled a major role for AQP5 in dynamic fine-tuning of the intracellular H2O2 concentration, and consequently in activating signaling networks related to cell survival and cancer progression, highlighting AQP5 as a promising drug target for cancer therapies.

scholarly journals Strength Through Unity: The Power of the Mega-Scaffold MACF1

2021 ◽  
Vol 9 ◽  
Author(s):  
Rebecca Cusseddu ◽  
Amélie Robert ◽  
Jean-François Côté
Keyword(s):  
Cell Migration ◽  
Cell Polarity ◽  
Tissue Homeostasis ◽  
Actin Microfilaments ◽  
Large Protein ◽  
Cellular Processes ◽  
Support Cell ◽  
Dynamic Events ◽  
Multiple Domains ◽  
Cytoskeletal Dynamic

The tight coordination of diverse cytoskeleton elements is required to support several dynamic cellular processes involved in development and tissue homeostasis. The spectraplakin-family of proteins are composed of multiple domains that provide versatility to connect different components of the cytoskeleton, including the actin microfilaments, microtubules and intermediates filaments. Spectraplakins act as orchestrators of precise cytoskeletal dynamic events. In this review, we focus on the prototypical spectraplakin MACF1, a protein scaffold of more than 700 kDa that coordinates the crosstalk between actin microfilaments and microtubules to support cell-cell connections, cell polarity, vesicular transport, proliferation, and cell migration. We will review over two decades of research aimed at understanding the molecular, physiological and pathological roles of MACF1, with a focus on its roles in developmental and cancer. A deeper understanding of MACF1 is currently limited by technical challenges associated to the study of such a large protein and we discuss ideas to advance the field.

scholarly journals Deciphering the Role of Endolysosomal Ca2+ Channels in Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Abeer F. Alharbi ◽  
John Parrington
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Cell Function ◽  
Immune Cell ◽  
Innate And Adaptive Immunity ◽  
Adaptive Immune ◽  
Physiological Processes ◽  
And Migration ◽  
Ca2 Channels

The role of endolysosomal Ca2+ signalling in immunity has been a subject of increasing interest in recent years. Here, we discuss evolving knowledge relating to the contribution of endolysosomal Ca2+ channels that include TPCs, TRPMLs, and P2X4R in physiological processes related to innate and adaptive immunity—including phagocytosis, inflammation, cytokine/chemokine release, dendritic, natural killer, and T cell activation and migration—and we underscore the paucity of clinical studies in this field. Emerging biomedical and translational data have led to important new insights into the critical roles of these channels in immune cell function and the regulation of innate and adaptive immune responses. The evolving immunological significance of endolysosomal Ca2+ signalling warrants further investigations to better characterize the roles of these channels in immunity in order to expand our knowledge about the pathology of inflammatory and autoimmune diseases and develop endolysosomal Ca2+ channels as viable biomarkers and therapeutic and preventive targets for remodelling the immune response.

scholarly journals Krüppel-like Factor 2 (KLF2) in Immune Cell Migration

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1171
Author(s):  
Jens Wittner ◽  
Wolfgang Schuh
Keyword(s):  
Transcription Factor ◽  
Cell Migration ◽  
Immune Responses ◽  
Adhesion Molecules ◽  
Chemokine Receptors ◽  
Immune Cell ◽  
Cell Types ◽  
Immune Cell Migration ◽  
Functional Relevance ◽  
And Migration

Krüppel-like factor 2 (KLF2), a transcription factor of the krüppel-like family, is a key regulator of activation, differentiation, and migration processes in various cell types. In this review, we focus on the functional relevance of KLF2 in immune cell migration and homing. We summarize the key functions of KLF2 in the regulation of chemokine receptors and adhesion molecules and discuss the relevance of the KLF2-mediated control of immune cell migration in the context of immune responses, infections, and diseases.

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