scholarly journals Critical role of lipid membranes in polarization and migration of cells: a biophysical view

2021 ◽  
Author(s):  
Erich Sackmann ◽  
Motomu Tanaka
Keyword(s):  
Cell Migration ◽  
Lipid Membranes ◽  
Cancer Metastasis ◽  
Membrane Surface ◽  
Critical Role ◽  
Biologically Relevant ◽  
Functional Roles ◽  
And Migration ◽  
Robust Regulation ◽  
Migration Of Cells

AbstractCell migration plays vital roles in many biologically relevant processes such as tissue morphogenesis and cancer metastasis, and it has fascinated biophysicists over the past several decades. However, despite an increasing number of studies highlighting the orchestration of proteins involved in different signaling pathways, the functional roles of lipid membranes have been essentially overlooked. Lipid membranes are generally considered to be a functionless two-dimensional matrix of proteins, although many proteins regulating cell migration gain functions only after they are recruited to the membrane surface and self-organize their functional domains. In this review, we summarize how the logistical recruitment and release of proteins to and from lipid membranes coordinates complex spatiotemporal molecular processes. As predicted from the classical framework of the Smoluchowski equation of diffusion, lipid/protein membranes serve as a 2D reaction hub that contributes to the effective and robust regulation of polarization and migration of cells involving several competing pathways.

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.

The integrin alphavbeta6 is critical for keratinocyte migration on both its known ligand, fibronectin, and on vitronectin

1998 ◽  
Vol 111 (15) ◽  
pp. 2189-2195 ◽  
Author(s):  
X. Huang ◽  
J. Wu ◽  
S. Spong ◽  
D. Sheppard
Keyword(s):  
Cell Migration ◽  
Tissue Injury ◽  
Critical Role ◽  
Cell Behavior ◽  
Wild Type ◽  
Migration Assays ◽  
And Migration ◽  
Hepatocyte Growth

The integrin alphavbeta6 is expressed on a variety of epithelial cells during dynamic processes including organogenesis, tissue injury and malignant transformation. However, because of the lack of tools to specifically inhibit the function of this integrin, little is known about its effects on cell behavior. To directly examine the role of this integrin in cell migration, we used keratinocytes derived from wild-type mice or mice expressing a null mutation in the beta6 subunit (beta6-/-) to perform migration assays in vitro. Migration on the known alphavbeta6 ligand, fibronectin was reduced in keratinocytes from beta6-/- mice. Interestingly, keratinocytes from beta6-/- mice also demonstrated markedly reduced migration on vitronectin, a protein not previously known to be a ligand for alphavbeta6. An anti-alphavbeta6 monoclonal antibody 10D5, generated by immunization of beta6-/- mice with murine keratinocytes, inhibited adhesion and migration of wild-type keratinocyte on both vitronectin and fibronectin to levels similar to those seen with keratinocytes from beta6-/- mice. alphavbeta6-mediated migration on both ligands was dramatically augmented by treatment with phorbol myrisate acetate (PMA) or with hepatocyte growth factor, and augmentation of migration by either stimulus could be abolished by the PKC inhibitor GF109203X, suggesting a critical role for PKC in enhancement of alphavbeta6-mediated cell migration.

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 Fascin limits Myosin activity within Drosophila border cells to control substrate stiffness and promote migration

2021 ◽  
Author(s):  
Maureen C. Lamb ◽  
Chathuri P. Kaluarachchi ◽  
Thiranjeewa I. Lansakara ◽  
Yiling Lan ◽  
Alexei V. Tivanski ◽  
...  
Keyword(s):  
Cell Migration ◽  
Nurse Cell ◽  
Cancer Metastasis ◽  
Critical Role ◽  
Substrate Stiffness ◽  
Cell Stiffness ◽  
Collective Cell Migration ◽  
Border Cells ◽  
Border Cell ◽  
Border Cell Migration

AbstractA key regulator of collective cell migrations, which drive development and cancer metastasis, is substrate stiffness. Increased substrate stiffness promotes migration and is controlled by Myosin. Using Drosophila border cell migration as a model of collective cell migration, we identify, for the first time, that the actin bundling protein Fascin limits Myosin activity in vivo. Loss of Fascin results in: increased activated Myosin on the border cells and their substrate, the nurse cells; decreased border cell Myosin dynamics; and increased nurse cell stiffness as measured by atomic force microscopy. Reducing Myosin restores on-time border cell migration in fascin mutant follicles. Further, Fascin’s actin bundling activity is required to limit Myosin activation. Surprisingly, we find that Fascin regulates Myosin activity in the border cells to control nurse cell stiffness to promote migration. Thus, these data shift the paradigm from a substrate stiffness-centric model of regulating migration, to uncover that collectively migrating cells play a critical role in controlling the mechanical properties of their substrate in order to promote their own migration. This new means of mechanical regulation of migration is likely conserved across contexts and organisms, as Fascin and Myosin are common regulators of cell migration.

scholarly journals HK2 Is a Crucial Downstream Regulator of miR-148a for the Maintenance of Sphere-Forming Property and Cisplatin Resistance in Cervical Cancer Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Hao Yang ◽  
Hui Hou ◽  
Haiping Zhao ◽  
Tianwei Yu ◽  
Yuchong Hu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Cancer Metastasis ◽  
Cisplatin Resistance ◽  
Critical Role ◽  
Cervical Cancer Cells ◽  
Enhanced Expression ◽  
And Migration ◽  
Sphere Formation

The acquisition of cancer stem-like properties is believed to be responsible for cancer metastasis and therapeutic resistance in cervical cancer (CC). CC tissues display a high expression level of hexokinase 2 (HK2), which is critical for the proliferation and migration of CC cells. However, little is known about the functional role of HK2 in the maintenance of cancer stem cell-like ability and cisplatin resistance of CC cells. Here, we showed that the expression of HK2 is significantly elevated in CC tissues, and high HK2 expression correlates with poor prognosis. HK2 overexpression (or knockdown) can promote (or inhibit) the sphere-forming ability and cisplatin resistance in CC cells. In addition, HK2-overexpressing CC cells show enhanced expression of cancer stem cell-associated genes (including SOX2 and OCT4) and drug resistance-related gene MDR1. The expression of HK2 is mediated by miR-145, miR-148a, and miR-497 in CC cells. Overexpression of miR-148a is sufficient to reduce sphere formation and cisplatin resistance in CC cells. Our results elucidate a novel mechanism through which miR-148a regulates CC stem cell-like properties and chemoresistance by interfering with the oncogene HK2, providing the first evidence that dysregulation of the miR-148a/HK2 signaling plays a critical role in the maintenance of sphere formation and cisplatin resistance of CC cells. Our findings may guide future studies on therapeutic strategies that reverse cisplatin resistance by targeting this pathway.

scholarly journals The interaction of Gα13 with integrin β1 mediates cell migration by dynamic regulation of RhoA

2015 ◽  
Vol 26 (20) ◽  
pp. 3658-3670 ◽  
Author(s):  
Bo Shen ◽  
Brian Estevez ◽  
Zheng Xu ◽  
Barry Kreutz ◽  
Andrei Karginov ◽  
...  
Keyword(s):  
Cell Migration ◽  
G Protein ◽  
Critical Role ◽  
Direct Interaction ◽  
Cytoplasmic Domain ◽  
Dynamic Regulation ◽  
Rhoa Activity ◽  
Dependent Cell ◽  
And Migration

Heterotrimeric G protein Gα13 is known to transmit G protein–coupled receptor (GPCR) signals leading to activation of RhoA and plays a role in cell migration. The mechanism underlying the role of Gα13 in cell migration, however, remains unclear. Recently we found that Gα13 interacts with the cytoplasmic domain of integrin β3 subunits in platelets via a conserved ExE motif. Here we show that a similar direct interaction between Gα13 and the cytoplasmic domain of the integrin β1 subunit plays a critical role in β1-dependent cell migration. Point mutation of either glutamic acid in the Gα13-binding 767EKE motif in β1 or treatment with a peptide derived from the Gα13-binding sequence of β1 abolished Gα13–β1 interaction and inhibited β1 integrin–dependent cell spreading and migration. We further show that the Gα13-β1 interaction mediates β1 integrin–dependent Src activation and transient RhoA inhibition during initial cell adhesion, which is in contrast to the role of Gα13 in mediating GPCR-dependent RhoA activation. These data indicate that Gα13 plays dynamic roles in both stimulating RhoA via a GPCR pathway and inhibiting RhoA via an integrin signaling pathway. This dynamic regulation of RhoA activity is critical for cell migration on β1 integrin ligands.

scholarly journals Research Progress for the Clinical Application of Circulating Tumor Cells in Prostate Cancer Diagnosis and Treatment

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Mei Yang ◽  
Xiaotian Zhang ◽  
Lixia Guo ◽  
Xiumin Liu ◽  
Jing Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Clinical Application ◽  
Cancer Metastasis ◽  
Critical Role ◽  
Response To Treatment ◽  
Research Progress ◽  
Diagnosis And Prognosis ◽  
And Migration

Prostate cancer is a life-threatening and highly heterogeneous malignancy. In the past decade, circulating tumor cells (CTCs) have been suggested to play a critical role in the occurrence and progression of prostate cancer. In particular, as the “seed” of the cancer metastasis cascade, CTCs determine numerous biological behaviors, such as tumor invasion into adjacent tissues and migration to distant organs. Many studies have shown that CTCs are necessary in the processes of tumor progression, including tumorigenesis, invasion, metastasis, and colonization. Furthermore, CTCs express various biomarkers relevant to prostate cancer and thus can be applied clinically in noninvasive tests. Moreover, CTCs can serve as potential prognostic targets in prostate cancer due to their roles in regulating many processes associated with cancer metastasis. In this review, we discuss the isolation and detection of CTCs as predictive markers of prostate cancer, and we discuss their clinical application in the diagnosis and prognosis of prostate cancer and in monitoring the response to treatment and the prediction of metastasis.

scholarly journals Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation

2019 ◽  
Author(s):  
Georgi Dimchev ◽  
Behnam Amiri ◽  
Ashley C. Humphries ◽  
Matthias Schaks ◽  
Vanessa Dimchev ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Polymerization ◽  
Binding Protein ◽  
Critical Role ◽  
Adhesion Formation ◽  
Leading Edge ◽  
Actin Binding ◽  
Membrane Ruffling ◽  
Genetic Ablation ◽  
And Migration

ABSTRACTEfficient migration on adhesive surfaces involves the protrusion of lamellipodial actin networks and their subsequent stabilization by nascent adhesions. The actin binding protein lamellipodin (Lpd) is thought to play a critical role in lamellipodium protrusion, by delivering Ena/VASP proteins onto the growing plus ends of actin filaments and by interacting with the WAVE regulatory complex (WRC), an activator of the Arp2/3 complex, at the leading edge. Using B16-F1 melanoma cell lines, we demonstrate that genetic ablation of Lpd compromises protrusion efficiency and coincident cell migration without altering essential parameters of lamellipodia, including their maximal rate of forward advancement and actin polymerization. We also confirmed lamellipodia and migration phenotypes with CRISPR/Cas9-mediated Lpd knockout Rat2 fibroblasts, excluding cell type-specific effects. Moreover, computer-aided analysis of cell edge morphodynamics on B16-F1 cell lamellipodia revealed that loss of Lpd correlates with reduced temporal protrusion maintenance as a prerequisite of nascent adhesion formation. We conclude that Lpd optimizes protrusion and nascent adhesion formation by counteracting frequent, chaotic retraction and membrane ruffling.Summary statementWe describe how genetic ablation of the prominent actin- and VASP-binding protein lamellipodin combined with software-aided protrusion analysis uncovers mechanistic insights into its cellular function during cell migration.

scholarly journals Long noncoding RNA ARHGAP5-AS1 inhibits migration of breast cancer cell via stabilizes SMAD7 protein

2020 ◽  
Author(s):  
Chen-Long Wang ◽  
Jing-Chi Li ◽  
Ci-Xiang Zhou ◽  
Cheng-Ning Ma ◽  
Di-Fei Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Noncoding Rna ◽  
Cancer Metastasis ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Functional Study ◽  
Breast Cancer Cell Lines

Abstract Background: Tumor metastasis is the main cause of death from breast cancer patients and cell migration plays a critical role in metastasis. Recent studies have shown long non-coding RNAs (lncRNAs) play an essential role in the initiation and progression of cancer. In the present study, the role of a LncRNA, ARHGAP5-AS1 in breast cancer was investigated.Methods: Bioinformation was analyzed for the expression of ARHGAP5-AS1. qRT-PCR was conducted to verify the expression of ARHGAP5-AS1 in breast cancer specimens. Transwell migration assays and F-actin staining were utilized to estimate cell migration ability. RNA pulldown assays and RNA immunoprecipitation were used to prove the interaction between ARHGAP5-AS1 and SMAD7. Western blot and immunofluorescence imaging were used to examine the protein levels. Dual luciferase reporter assays were performed to evaluate the activation of TGF-β signaling.Results: Compared to MDA-MB-231 cells, the expression of LncRNA ARHGAP5-AS1(NR_027263) was significantly suppressed in its highly metastatic subtype MDA-MB-231-LM2 cells. Functional study showed ARHGAP5-AS1 could inhibit cell migration via suppression of stress fibers in breast cancer cell lines. Afterwards, SMAD7 was further identified to interact with ARHGAP5-AS1 by its PY motif and thus its ubiquitination and degradation was blocked due to reduced interaction with E3 ligase SMURF1 and SMURF2. Moreover, ARHGAP5-AS1 could inhibit TGF-β signaling pathway due to its inhibitory role on SMAD7.Conclusions: Overall, these findings demonstrate that ARHGAP5-AS1 inhibits breast cancer cell migration and could server as a novel biomarker for breast cancer metastasis and a potent target for the treatment in the future.

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