scholarly journals Ca2+Signaling in Cytoskeletal Reorganization, Cell Migration, and Cancer Metastasis

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Feng-Chiao Tsai ◽  
Guan-Hung Kuo ◽  
Shu-Wei Chang ◽  
Pei-Ju Tsai
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Cell Motility ◽  
Cancer Metastasis ◽  
Leading Edge ◽  
Signaling Molecules ◽  
Structural Components ◽  
Cytoskeletal Reorganization ◽  
The Right ◽  
Persistent Cell

Proper control of Ca2+signaling is mandatory for effective cell migration, which is critical for embryonic development, wound healing, and cancer metastasis. However, how Ca2+coordinates structural components and signaling molecules for proper cell motility had remained elusive. With the advance of fluorescent live-cell Ca2+imaging in recent years, we gradually understand how Ca2+is regulated spatially and temporally in migrating cells, driving polarization, protrusion, retraction, and adhesion at the right place and right time. Here we give an overview about how cells create local Ca2+pulses near the leading edge, maintain cytosolic Ca2+gradient from back to front, and restore Ca2+depletion for persistent cell motility. Differential roles of Ca2+in regulating various effectors and the interaction of roles of Ca2+signaling with other pathways during migration are also discussed. Such information might suggest a new direction to control cancer metastasis by manipulating Ca2+and its associating signaling molecules in a judicious manner.

Nanotopography-Modulated Epithelial Cell Collective Migration

2021 ◽  
Vol 17 (6) ◽  
pp. 1079-1087
Author(s):  
Zaozao Chen ◽  
Qiwei Li ◽  
Shihui Xu ◽  
Jun Ouyang ◽  
Hongmei Wei
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Epithelial Cells ◽  
Leading Edge ◽  
Cell Types ◽  
Protein Kinase Activity ◽  
Migration Behavior ◽  
Collective Migration ◽  
Epithelial Migration ◽  
Activity Dependent

Matrix nanotopography plays an essential role in regulating cell behaviors including cell proliferation, differentiation, and migration. While studies on isolated single cell migration along the nanostructural orientation have been reported for various cell types, there remains a lack of understanding of how nanotopography regulates the behavior of collectively migrating cells during processes such as epithelial wound healing. We demonstrated that collective migration of epithelial cells was promoted on nanogratings perpendicular to, but not on those parallel to, the wound-healing axis. We further discovered that nanograting-modulated epithelial migration was dominated by the adhesion turnover process, which was Rho-associated protein kinase activity-dependent, and the lamellipodia protrusion at the cell leading edge, which was Rac1-GTPase activity-dependent. This work provides explanations to the distinct migration behavior of epithelial cells on nanogratings, and indicates that the effect of nanotopographic modulations on cell migration is cell-type dependent and involves complex mechanisms

scholarly journals Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Regulates Actin Organization and Cell Motility by Phosphorylating the Actin Cross-Linking Protein EPLIN

2007 ◽  
Vol 27 (23) ◽  
pp. 8190-8204 ◽  
Author(s):  
Mei-Ying Han ◽  
Hidetaka Kosako ◽  
Toshiki Watanabe ◽  
Seisuke Hattori
Keyword(s):  
Wound Healing ◽  
Cell Migration ◽  
Cell Motility ◽  
Stress Fiber ◽  
Mitogen Activated Protein Kinase ◽  
Cross Linking ◽  
Intact Cells ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

ABSTRACT Extracellular signal-regulated kinase (ERK) is important for various cellular processes, including cell migration. However, the detailed molecular mechanism by which ERK promotes cell motility remains elusive. Here we characterize epithelial protein lost in neoplasm (EPLIN), an F-actin cross-linking protein, as a novel substrate for ERK. ERK phosphorylates Ser360, Ser602, and Ser692 on EPLIN in vitro and in intact cells. Phosphorylation of the C-terminal region of EPLIN reduces its affinity for actin filaments. EPLIN colocalizes with actin stress fibers in quiescent cells, and stimulation with platelet-derived growth factor (PDGF) induces stress fiber disassembly and relocalization of EPLIN to peripheral and dorsal ruffles, wherein phosphorylation of Ser360 and Ser602 is observed. Phosphorylation of these two residues is also evident during wound healing at the leading edge of migrating cells. Moreover, expression of a non-ERK-phosphorylatable mutant, but not wild-type EPLIN, prevents PDGF-induced stress fiber disassembly and membrane ruffling and also inhibits wound healing and PDGF-induced cell migration. We propose that ERK-mediated phosphorylation of EPLIN contributes to actin filament reorganization and enhanced cell motility.

scholarly journals Pak1 regulates focal adhesion strength, myosin IIA distribution, and actin dynamics to optimize cell migration

2011 ◽  
Vol 193 (7) ◽  
pp. 1289-1303 ◽  
Author(s):  
Violaine D. Delorme-Walker ◽  
Jeffrey R. Peterson ◽  
Jonathan Chernoff ◽  
Clare M. Waterman ◽  
Gaudenz Danuser ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Adhesion Strength ◽  
Focal Adhesion ◽  
Leading Edge ◽  
Actin Dynamics ◽  
Filamentous Actin ◽  
Downstream Effectors ◽  
Myosin Iia ◽  
And Migration

Cell motility requires the spatial and temporal coordination of forces in the actomyosin cytoskeleton with extracellular adhesion. The biochemical mechanism that coordinates filamentous actin (F-actin) assembly, myosin contractility, adhesion dynamics, and motility to maintain the balance between adhesion and contraction remains unknown. In this paper, we show that p21-activated kinases (Paks), downstream effectors of the small guanosine triphosphatases Rac and Cdc42, biochemically couple leading-edge actin dynamics to focal adhesion (FA) dynamics. Quantitative live cell microscopy assays revealed that the inhibition of Paks abolished F-actin flow in the lamella, displaced myosin IIA from the cell edge, and decreased FA turnover. We show that, by controlling the dynamics of these three systems, Paks regulate the protrusive activity and migration of epithelial cells. Furthermore, we found that expressing Pak1 was sufficient to overcome the inhibitory effects of excess adhesion strength on cell motility. These findings establish Paks as critical molecules coordinating cytoskeletal systems for efficient cell migration.

scholarly journals Mechanochemical coupling and junctional forces during collective cell migration

2019 ◽  
Author(s):  
J. Bui ◽  
D. E. Conway ◽  
R. L. Heise ◽  
S.H. Weinberg
Keyword(s):  
Cell Migration ◽  
Rho Gtpases ◽  
Cancer Metastasis ◽  
Rho Gtpase ◽  
Critical Role ◽  
Leading Edge ◽  
Collective Cell Migration ◽  
Gtpase Activity ◽  
Modeling Framework ◽  
Cell Cell

ABSTRACTCell migration, a fundamental physiological process in which cells sense and move through their surrounding physical environment, plays a critical role in development and tissue formation, as well as pathological processes, such as cancer metastasis and wound healing. During cell migration, dynamics are governed by the bidirectional interplay between cell-generated mechanical forces and the activity of Rho GTPases, a family of small GTP-binding proteins that regulate actin cytoskeleton assembly and cellular contractility. These interactions are inherently more complex during the collective migration of mechanically coupled cells, due to the additional regulation of cell-cell junctional forces. In this study, we present a minimal modeling framework to simulate the interactions between mechanochemical signaling in individual cells and interactions with cell-cell junctional forces during collective cell migration. We find that migration of individual cells depends on the feedback between mechanical tension and Rho GTPase activity in a biphasic manner. During collective cell migration, waves of Rho GTPase activity mediate mechanical contraction/extension and thus synchronization throughout the tissue. Further, cell-cell junctional forces exhibit distinct spatial patterns during collective cell migration, with larger forces near the leading edge. Larger junctional force magnitudes are associated with faster collective cell migration and larger tissue size. Simulations of heterogeneous tissue migration exhibit a complex dependence on the properties of both leading and trailing cells. Computational predictions demonstrate that collective cell migration depends on both the emergent dynamics and interactions between cellular-level Rho GTPase activity and contractility, and multicellular-level junctional forces.

scholarly journals Pointed-end capping by tropomodulin3 negatively regulates endothelial cell motility

2003 ◽  
Vol 161 (2) ◽  
pp. 371-380 ◽  
Author(s):  
Robert S. Fischer ◽  
Kimberly L. Fritz-Six ◽  
Velia M. Fowler
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Actin Filament ◽  
Actin Filaments ◽  
Critical Role ◽  
Leading Edge ◽  
Average Cell ◽  
Transient Overexpression ◽  
End Capping ◽  
Pointed End

Actin filament pointed-end dynamics are thought to play a critical role in cell motility, yet regulation of this process remains poorly understood. We describe here a previously uncharacterized tropomodulin (Tmod) isoform, Tmod3, which is widely expressed in human tissues and is present in human microvascular endothelial cells (HMEC-1). Tmod3 is present in sufficient quantity to cap pointed ends of actin filaments, localizes to actin filament structures in HMEC-1 cells, and appears enriched in leading edge ruffles and lamellipodia. Transient overexpression of GFP–Tmod3 leads to a depolarized cell morphology and decreased cell motility. A fivefold increase in Tmod3 results in an equivalent decrease in free pointed ends in the cells. Unexpectedly, a decrease in the relative amounts of F-actin, free barbed ends, and actin-related protein 2/3 (Arp2/3) complex in lamellipodia are also observed. Conversely, decreased expression of Tmod3 by RNA interference leads to faster average cell migration, along with increases in free pointed and barbed ends in lamellipodial actin filaments. These data collectively demonstrate that capping of actin filament pointed ends by Tmod3 inhibits cell migration and reveal a novel control mechanism for regulation of actin filaments in lamellipodia.

The role of vesicle trafficking in epithelial cell motility

2009 ◽  
Vol 37 (5) ◽  
pp. 1072-1076 ◽  
Author(s):  
Sarah J. Fletcher ◽  
Joshua Z. Rappoport
Keyword(s):  
Wound Healing ◽  
Epithelial Cell ◽  
Cell Motility ◽  
Cancer Metastasis ◽  
Endosomal Recycling ◽  
Epithelial Cell Migration ◽  
Polarized Trafficking ◽  
Epithelial Wound Healing ◽  
Relevant Topic

Cell motility is important for many physiological and pathological processes including organ development, wound healing, cancer metastasis and correct immune responses. In particular, epithelial wound healing is both a medically relevant topic and a common experimental model. Mechanisms underlying generation of a polarized cell and maintenance of a motile phenotype during steady-state migration are not well understood. Polarized trafficking of bulk membrane and cell adhesion molecules has been implicated in regulation of cell motility. The present review focuses on the role of different trafficking pathways in epithelial cell migration, including clathrin-mediated endocytosis, caveolar endocytosis, exocytosis of biosynthetic cargo, ‘short-loop’ and ‘long-loop’ endosomal recycling.

The Influence of Polymeric Fiber Stiffness and Alignment on Cytoplasmic Bleb Dynamics and Migration of Glioblastoma Multiforme Cells

2012 ◽  
Author(s):  
Puja Sharma ◽  
Kevin Sheets ◽  
Amrinder S. Nain
Keyword(s):  
Immune Response ◽  
Wound Healing ◽  
Cell Migration ◽  
Glioblastoma Multiforme ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Hallmarks Of Cancer ◽  
Multistep Process ◽  
And Migration ◽  
Polymeric Fiber

Cell migration is a tightly regulated phenomenon necessary for regular physiologic processes such as wound healing, immune response, embryonic development, growth, and regeneration [1–3]. Consequences of abnormal migratory behaviors include autoimmune diseases and metastasis during cancer progression [4, 5]. Described as one of the hallmarks of cancer, metastasis is a complex multistep process, and is responsible for 90% of cancer deaths in humans. A better understanding of the process of metastasis is of paramount importance in developing efficient cancer treatment therapies and drugs [6].

scholarly journals Phosphorylation of Tyrosine Residues 31 and 118 on Paxillin Regulates Cell Migration through an Association with Crk in Nbt-II Cells

2000 ◽  
Vol 148 (5) ◽  
pp. 957-970 ◽  
Author(s):  
Valérie Petit ◽  
Brigitte Boyer ◽  
Delphine Lentz ◽  
Christopher E. Turner ◽  
Jean Paul Thiery ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Critical Role ◽  
Adaptor Protein ◽  
Signaling Molecules ◽  
Sh2 Domain ◽  
Wild Type ◽  
Tyrosine Residues ◽  
Pathological Conditions

Identification of signaling molecules that regulate cell migration is important for understanding fundamental processes in development and the origin of various pathological conditions. The migration of Nara Bladder Tumor II (NBT-II) cells was used to determine which signaling molecules are specifically involved in the collagen-mediated locomotion. We show here that paxillin is tyrosine phosphorylated after induction of motility on collagen. Overexpression of paxillin mutants in which tyrosine 31 and/or tyrosine 118 were replaced by phenylalanine effectively impaired cell motility. Moreover, stimulation of motility by collagen preferentially enhanced the association of paxillin with the SH2 domain of the adaptor protein CrkII. Mutations in both tyrosine 31 and 118 diminished the phosphotyrosine content of paxillin and prevented the formation of the paxillin–Crk complex, suggesting that this association is necessary for collagen-mediated NBT-II cell migration. Other responses to collagen, such as cell adhesion and spreading, were not affected by these mutations. Overexpression of wild-type paxillin or Crk could bypass the migration-deficient phenotype. Both the SH2 and the SH3 domains of CrkII are shown to play a critical role in this collagen-mediated migration. These results demonstrate the important role of the paxillin–Crk complex in the collagen-induced cell motility.

scholarly journals Local Myo9b RhoGAP activity regulates cell motility

2020 ◽  
pp. jbc.RA120.013623
Author(s):  
Sandra Angela Hemkemeyer ◽  
Veith Vollmer ◽  
Vera Schwarz ◽  
Birgit Lohmann ◽  
Ulrike Honnert ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Cell Morphology ◽  
Actin Polymerization ◽  
Rho Gtpase ◽  
Leading Edge ◽  
Cell Extension ◽  
Local Inhibition ◽  
And Migration ◽  
Directional Cell Migration

To migrate, cells assume a polarized morphology, extending forward with a leading edge with their trailing edge retracting back toward the cell body. Both cell extension and retraction critically depend on the organization and dynamics of the actin cytoskeleton, and the small, monomeric GTPases Rac and Rho are important regulators of actin. Activation of Rac induces actin polymerization and cell extension whereas activation of Rho enhances acto-myosin II contractility and cell retraction. To coordinate migration, these processes must be carefully regulated. The myosin Myo9b, a Rho GTPase activating protein (GAP), negatively regulates Rho activity and deletion of Myo9b in leukocytes impairs cell migration through increased Rho activity. However, it is not known whether cell motility is regulated by global or local inhibition of Rho activity by Myo9b. Here, we addressed this question by using Myo9b-deficient macrophage-like cells that expressed different recombinant Myo9b constructs. We found that Myo9b accumulates in lamellipodial extensions generated by Rac-induced actin polymerization as a function of its motor activity. Deletion of Myo9b in HL-60 derived macrophages altered cell morphology and impaired cell migration. Reintroduction of Myo9b or Myo9b motor and GAP mutants revealed that local GAP activity rescues cell morphology and migration. In summary, Rac activation leads to actin polymerization and recruitment of Myo9b, which locally inhibits Rho activity to enhance directional cell migration. In summary, Rac activation leads to actin polymerization and recruitment of Myo9b, which locally inhibits Rho activity to enhance directional cell migration.

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