Involvement of Rho GAP GRAF1 in maintenance of epithelial phenotype.

Abstract:

:Adhesion of epithelial cell to each other and to extracellular matrix, as well as cell migration ability and cytoskeleton organization undergo significant alterations in the course of neoplastic transformation, but regulatory mechanisms involved in these processes are not fully understood. Here, we studied the role of a Rho GAP protein GRAF1 (GTPase Regulator Associated with Focal adhesion kinase-1) in the regulation of the epithelial phenotype in cells of breast derived, non-malignant, MCF10A cell line. GRAF1 was shown to be localized to cell-cell junctions, and its depletion resulted in accelerated cell migration velocity, elongation of the cells and cell colonies, impaired monolayer integrity and significant disruption of desmosomes with a loss of associated keratin filaments. These processes were accompanied by formation of larger focal adhesions, an increased number of contractile actin stress fibers, reduction in epithelial markers and increase in mesenchymal markers such as epithelial-mesenchymal transition (EMT)-specific transcription factors Snail-1 and Snail-2, as well as N-cadherin, and vimentin. Moreover, unlike control cells, GRAF1 knocked-down cells demonstrated anchorage-independent growth in soft agar. GRAF1 expression in several highly invasive breast cancer cell lines was low, as compared to the non-malignant MCF10A cells, while overexpressing of GRAF1 in the malignant BT-549 cell line led to a decrease of mesenchymal markers, especially the Snail-1 and 2. Altogether, our analysis suggests that GRAF1 plays a role in the maintenance of normal epithelial phenotype and its depletion leads to an EMT-like process that might be involved in neoplastic transformation.

journal_name

Cell Adh Migr

authors

Regev M,Sabanay H,Kartvelishvily E,Kam Z,Bershadsky AD

doi

10.1080/19336918.2016.1227910

subject

Has Abstract

pub_date

2017-07-04 00:00:00

pages

367-383

issue

4

eissn

1933-6918

issn

1933-6926

journal_volume

11

pub_type

杂志文章
  • Spatial and temporal coordination of traction forces in one-dimensional cell migration.

    abstract::Migration of a fibroblast along a collagen fiber can be regarded as cell locomotion in one-dimension (1D). In this process, a cell protrudes forward, forms a new adhesion, produces traction forces, and releases its rear adhesion in order to advance itself along a path. However, how a cell coordinates its adhesion form...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章

    doi:10.1080/19336918.2016.1221563

    authors: Han SJ,Rodriguez ML,Al-Rekabi Z,Sniadecki NJ

    更新日期:2016-09-02 00:00:00

  • The tumor suppressor gene ARHI (DIRAS3) inhibits ovarian cancer cell migration through multiple mechanisms.

    abstract::ARHI is an imprinted tumor suppressor gene that is downregulated in > 60% of ovarian cancers, associated with decreased progression-free survival. ARHI encodes a 26 kDa GTPase with homology to Ras. Re-expression of ARHI inhibits ovarian cancer growth, initiates autophagy and induces tumor dormancy. Recent studies have...

    journal_title:Cell adhesion & migration

    pub_type: 评论,杂志文章

    doi:10.4161/cam.23648

    authors: Lu Z,Bast RC Jr

    更新日期:2013-03-01 00:00:00

  • Diversity in the molecular and cellular strategies of epithelium-to-mesenchyme transitions: Insights from the neural crest.

    abstract::Although epithelial to mesenchymal transitions (EMT) are often viewed as a unique event, they are characterized by a great diversity of cellular processes resulting in strikingly different outcomes. They may be complete or partial, massive or progressive, and lead to the complete disruption of the epithelium or leave ...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章

    doi:10.4161/cam.4.3.12501

    authors: Duband JL

    更新日期:2010-07-01 00:00:00

  • Par6 is phosphorylated by aPKC to facilitate EMT.

    abstract::The conserved polarity proteins Par6 and aPKC regulate cell polarization processes. However, increasing evidence also suggests that they play a role in oncogenic progression. During tumor progression, epithelial to mesenchymal transition (EMT) delineates an evolutionary conserved process that converts stationary epith...

    journal_title:Cell adhesion & migration

    pub_type: 评论,杂志文章

    doi:10.4161/cam.25651

    authors: Gunaratne A,Di Guglielmo GM

    更新日期:2013-07-01 00:00:00

  • Molecular signaling blockade as a new approach to inhibit leukocyte-endothelial interactions for inflammatory bowel disease treatment.

    abstract::Mitogen-activated protein kinases (MAPK) are among the major widespread transduction pathways in humans. They are involved in several inflammatory disorders, including the pathogenesis of inflammatory bowel disease (IBD). A recent paper showed that activated MAPK are upregulated on endothelium and fibroblasts from int...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章

    doi:10.4161/cam.3.3.9152

    authors: Scaldaferri F,Correale C,Gasbarrini A,Danese S

    更新日期:2009-07-01 00:00:00

  • Protein tyrosine phosphatase PTP1B in cell adhesion and migration.

    abstract::Cell migration requires a highly coordinated interplay between specialized plasma membrane adhesion complexes and the cytoskeleton. Protein phosphorylation/dephosphorylation modifications regulate many aspects of the integrin-cytoskeleton interdependence, including their coupling, dynamics, and organization to support...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章

    doi:10.4161/cam.26375

    authors: Arregui CO,González Á,Burdisso JE,González Wusener AE

    更新日期:2013-09-01 00:00:00

  • Emerging roles of the tumor-associated stroma in promoting tumor metastasis.

    abstract::The stroma in human carcinomas consists of extracellular matrix and various types of non-carcinoma cells, mainly leukocytes, endothelial cells, fibroblasts, myofibroblasts and bone marrow-derived progenitors. The tumor-associated stroma actively supports tumor growth by stimulating neo-angiogenesis, as well as prolife...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章,评审

    doi:10.4161/cam.20631

    authors: Horimoto Y,Polanska UM,Takahashi Y,Orimo A

    更新日期:2012-05-01 00:00:00

  • EphA2 promotes cell adhesion and spreading of monocyte and monocyte/macrophage cell lines on integrin ligand-coated surfaces.

    abstract::Eph signaling, which arises following stimulation by ephrins, is known to induce opposite cell behaviors such as promoting and inhibiting cell adhesion as well as promoting cell-cell adhesion and repulsion by altering the organization of the actin cytoskeleton and influencing the adhesion activities of integrins. Howe...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章

    doi:10.1080/19336918.2015.1107693

    authors: Saeki N,Nishino S,Shimizu T,Ogawa K

    更新日期:2015-01-01 00:00:00

  • Occupy tissue: the movement in cancer metastasis.

    abstract::The critical role of migration and invasion in cancer metastasis warrants new therapeutic approaches targeting the machinery regulating cell migration and invasion. While 2-dimensional (2D) models have helped identify a range of adhesion molecules, cytoskeletal components and regulators that are potentially important ...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章,评审

    doi:10.4161/cam.21559

    authors: Bradbury P,Fabry B,O'Neill GM

    更新日期:2012-09-01 00:00:00

  • Sweet cues: How heparan sulfate modification of fibronectin enables growth factor guided migration of embryonic cells.

    abstract::Growth factors regulate a diverse array of cellular functions including proliferation, survival, movement, and the ability to do this often involves interactions with the extracellular matrix (ECM) and particularly heparan sulfate proteoglycans (HSPGs). HSPGs have been shown to sequester growth factors, and to act as ...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章

    doi:10.4161/cam.4.4.12427

    authors: Symes K,Smith EM,Mitsi M,Nugent MA

    更新日期:2010-10-01 00:00:00

  • The interplay between extracellular matrix remodelling and kinase signalling in cancer progression and metastasis.

    abstract::The extracellular matrix (ECM) is a master regulator of cellular phenotype and behaviour. It plays a crucial role in both normal tissue homeostasis and complex diseases such as cancer. The interplay between the intrinsic factors of cancer cells themselves, including their genotype and signalling networks; and the extr...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章,评审

    doi:10.1080/19336918.2017.1405208

    authors: Skhinas JN,Cox TR

    更新日期:2018-01-01 00:00:00

  • Laminin α5 guides tissue patterning and organogenesis.

    abstract::Laminins (LM) are extracellular matrix molecules that contribute to and are required for the formation of basement membranes. They participate in the modulation of epithelial/mesenchymal interactions and are implicated in organogenesis and maintenance of organ homeostasis. Among the LM molecules, the LM α5 chain (LMα5...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章,评审

    doi:10.4161/cam.22236

    authors: Spenlé C,Simon-Assmann P,Orend G,Miner JH

    更新日期:2013-01-01 00:00:00

  • Cdk5: A regulator of epithelial cell adhesion and migration.

    abstract::Cell adhesion is a fundamental property of epithelial cells required for anchoring, migration and survival. During cell migration, the formation and disruption of adhesion sites is stringently regulated by integration of multiple, sequential signals acting in distinct regions of the cell. Recent findings implicate cyc...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章

    doi:10.4161/cam.4.3.11131

    authors: Tripathi BK,Zelenka PS

    更新日期:2010-07-01 00:00:00

  • Navigating the cell: UNC-53 and the navigators, a family of cytoskeletal regulators with multiple roles in cell migration, outgrowth and trafficking.

    abstract::Changes in cell shape are associated with a variety of processes including cell migration, axon outgrowth, cell division and vesicle trafficking. C. elegans UNC-53 and its vertebrate homologs, the Navigators, are required for the migration of cells and the outgrowth of neuronal processes. The identification of novel m...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章,评审

    doi:10.4161/cam.3.4.9451

    authors: Stringham EG,Schmidt KL

    更新日期:2009-10-01 00:00:00

  • "Armed" oncolytic herpes simplex viruses for brain tumor therapy.

    abstract::Genetically engineered, conditionally replicating herpes simplex viruses type 1 (HSV-1) are promising therapeutic agents for brain tumors and other solid cancers. They can replicate in situ, spread and exhibit oncolytic activity via a direct cytocidal effect. One of the advantages of HSV-1 is the capacity to incorpora...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章

    doi:10.4161/cam.2.3.6353

    authors: Todo T

    更新日期:2008-07-01 00:00:00

  • Controlling matrix stiffness and topography for the study of tumor cell migration.

    abstract::Cellular studies have long been performed on the bench top, within Petri dishes and flasks that expose cells to surroundings that differ greatly from their native environment. The complexity of a human tissue is such that to truly replicate a cell's physiologic microenvironment in vitro is currently impossible. It is ...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章,评审

    doi:10.4161/cam.21076

    authors: Kraning-Rush CM,Reinhart-King CA

    更新日期:2012-05-01 00:00:00

  • The influence of biomechanical properties and cannabinoids on tumor invasion.

    abstract:BACKGROUND:Cannabinoids are known to have an anti-tumorous effect, but the underlying mechanisms are only sparsely understood. Mechanical characteristics of tumor cells represent a promising marker to distinguish between tumor cells and the healthy tissue. We tested the hypothesis whether cannabinoids influence the tum...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章

    doi:10.1080/19336918.2016.1183867

    authors: Hohmann T,Grabiec U,Ghadban C,Feese K,Dehghani F

    更新日期:2017-01-02 00:00:00

  • Glial and axonal regeneration following spinal cord injury.

    abstract::Spinal cord injury (SCI) has been regarded clinically as an irreversible damage caused by tissue contusion due to a blunt external force. Past research had focused on the analysis of the pathogenesis of secondary injury that extends from the injury epicenter to the periphery, as well as tissue damage and neural cell d...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章,评审

    doi:10.4161/cam.3.1.7372

    authors: Shibuya S,Yamamoto T,Itano T

    更新日期:2009-01-01 00:00:00

  • Stretching the timescale of intravital imaging in tumors.

    abstract::Since the time it was pioneered in 1992, intravital imaging of tumors at cellular resolution has offered us the extremely important opportunity of "seeing biology." However, until now, most studies were monitoring tumor cell behavior in the same animal over short times, requiring the combining of acquired data into a ...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章

    doi:10.4161/cam.3.4.9581

    authors: Gligorijevic B,Condeelis J

    更新日期:2009-10-01 00:00:00

  • Spatiotemporal organization and mechanosensory function of podosomes.

    abstract::Podosomes are small, circular adhesions formed by cells such as osteoclasts, macrophages, dendritic cells, and endothelial cells. They comprise a protrusive actin core module and an adhesive ring module composed of integrins and cytoskeletal adaptor proteins such as vinculin and talin. Furthermore, podosomes are assoc...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章,评审

    doi:10.4161/cam.28182

    authors: van den Dries K,Bolomini-Vittori M,Cambi A

    更新日期:2014-01-01 00:00:00

  • Single cell rigidity sensing: A complex relationship between focal adhesion dynamics and large-scale actin cytoskeleton remodeling.

    abstract::Many physiological and pathological processes involve tissue cells sensing the rigidity of their environment. In general, tissue cells have been shown to react to the stiffness of their environment by regulating their level of contractility, and in turn applying traction forces on their environment to probe it. This m...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章,评审

    doi:10.1080/19336918.2016.1173800

    authors: Gupta M,Doss B,Lim CT,Voituriez R,Ladoux B

    更新日期:2016-09-02 00:00:00

  • Foxc2 transcription factor as a regulator of angiogenesis via induction of integrin beta3 expression.

    abstract::Angiogenesis, the growth of new blood vessels from pre-existing vessels, is a process involving endothelial cell proliferation, migration and vascular tube formation. One of the key molecules that regulate this process is the integrin beta3 subunit, a cell adhesion receptor that forms a heterodimer with the integrin a...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章

    doi:10.4161/cam.3.1.7252

    authors: Hayashi H,Kume T

    更新日期:2009-01-01 00:00:00

  • Role of glycosylation in hypoxia-driven cell migration and invasion.

    abstract::Hypoxia, a common condition of the tumor microenvironment, induces changes in the proteome of cancer cells, mainly via HIF-1, a transcription factor conformed by a constitutively expressed β-subunit and an oxygen-regulated α-subunit. In hypoxia, HIF-1α stabilizes, forms the heterodimeric complex with HIF-1β, and binds...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章,评审

    doi:10.1080/19336918.2018.1491234

    authors: Arriagada C,Silva P,Torres VA

    更新日期:2019-12-01 00:00:00

  • Monitoring the dynamics of Src activity in response to anti-invasive dasatinib treatment at a subcellular level using dual intravital imaging.

    abstract::Optimising response to tyrosine kinase inhibitors in cancer remains an extensive field of research. Intravital imaging is an emerging tool, which can be used in drug discovery to facilitate and fine-tune maximum drug response in live tumors. A greater understanding of intratumoural delivery and pharmacodynamics of a d...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章

    doi:10.4161/19336918.2014.970004

    authors: Nobis M,McGhee EJ,Herrmann D,Magenau A,Morton JP,Anderson KI,Timpson P

    更新日期:2014-01-01 00:00:00

  • The multifaceted roles of Eph/ephrin signaling in breast cancer.

    abstract::Eph receptors and their membrane-bound ligands are intimately involved in the control of morphogenic processes during embryonic development and adult tissue homeostasis. By their ability to orchestrate cell migration, pattern formation and tissue integrity they are also prone to be involved in carcinogenic growth. In ...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章,评审

    doi:10.4161/cam.20154

    authors: Kaenel P,Mosimann M,Andres AC

    更新日期:2012-03-01 00:00:00

  • NAD and axon degeneration: from the Wlds gene to neurochemistry.

    abstract::Neurodegenerative diseases have become a global issue due to the aging population. These disorders affect a vast patient population and represent a huge area of unmet therapeutic need. Axon degeneration is a common pathological character of those neurodegenerative diseases. It results in the loss of communication betw...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章,评审

    doi:10.4161/cam.3.1.7483

    authors: Wang J,He Z

    更新日期:2009-01-01 00:00:00

  • Unexpected role of lipocalin-type prostaglandin D synthase in brain: regulation of glial cell migration and morphology.

    abstract::Lipocalin-type prostaglandin D synthase (L-PGDS) is one of the most abundant proteins in the cerebrospinal fluid. Nevertheless, its role in the central nervous system is far from clear. Here, we present evidence that L-PGDS induces glial cell migration and morphological changes in vitro and in vivo. We also identified...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章

    doi:10.4161/cam.20251

    authors: Suk K

    更新日期:2012-05-01 00:00:00

  • Invadopodia and basement membrane invasion in vivo.

    abstract::Over 20 years ago, protrusive, F-actin-based membrane structures, termed invadopodia, were identified in highly metastatic cancer cell lines. Invadopodia penetrate artificial or explanted extracellular matrices in 2D culture conditions and have been hypothesized to facilitate the migration of cancer cells through base...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章,评审

    doi:10.4161/cam.28406

    authors: Lohmer LL,Kelley LC,Hagedorn EJ,Sherwood DR

    更新日期:2014-01-01 00:00:00

  • Diversification of caldesmon-linked actin cytoskeleton in cell motility.

    abstract::The actin cytoskeleton plays a key role in regulating cell motility. Caldesmon (CaD) is an actin-linked regulatory protein found in smooth muscle and non-muscle cells that is conserved among a variety of vertebrates. It binds and stabilizes actin filaments, as well as regulating actin-myosin interaction in a calcium (...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章,评审

    doi:10.4161/cam.5.2.14398

    authors: Mayanagi T,Sobue K

    更新日期:2011-03-01 00:00:00

  • Paxillin controls directional cell motility in response to physical cues.

    abstract::Physical cues from the extracellular environment that influence cell shape and directional migration are transduced into changes in cytoskeletal organization and biochemistry through integrin-based cell adhesions to extracellular matrix (ECM). Paxillin is a focal adhesion (FA) scaffold protein that mediates integrin a...

    journal_title:Cell adhesion & migration

    pub_type: 杂志文章

    doi:10.4161/cam.21672

    authors: Sero JE,German AE,Mammoto A,Ingber DE

    更新日期:2012-11-01 00:00:00