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Cells Aug 2022Cell cycle and cell adhesion are two interdependent cellular processes regulating each other, reciprocally, in every cell cycle phase. The cell adhesion to the... (Review)
Review
Cell cycle and cell adhesion are two interdependent cellular processes regulating each other, reciprocally, in every cell cycle phase. The cell adhesion to the extracellular matrix (ECM) via integrin receptors triggers signaling pathways required for the cell cycle progression; the passage from the G1 to S phase and the completion of cytokinesis are the best-understood events. Growing evidence, however, suggests more adhesion-dependent regulatory aspects of the cell cycle, particularly during G2 to M transition and early mitosis. Conversely, the cell cycle machinery regulates cell adhesion in manners recently shown driven mainly by cyclin-dependent kinase 1 (CDK1). This review summarizes the recent findings regarding the role of integrin-mediated cell adhesion and its downstream signaling components in regulating the cell cycle, emphasizing the cell cycle progression through the G2 and early M phases. Further investigations are required to raise our knowledge about the molecular mechanisms of crosstalk between cell adhesion and the cell cycle in detail.
Topics: Cell Adhesion; Cell Cycle; Cell Cycle Checkpoints; Integrins; Mitosis
PubMed: 36010598
DOI: 10.3390/cells11162521 -
Journal of Visualized Experiments : JoVE May 2011Studies of cell-cell cohesion and cell-substratum adhesion have historically been performed on monolayer cultures adherent to rigid substrates. Cells within a tissue,...
Studies of cell-cell cohesion and cell-substratum adhesion have historically been performed on monolayer cultures adherent to rigid substrates. Cells within a tissue, however, are typically encased within a closely packed tissue mass in which cells establish intimate connections with many near-neighbors and with extracellular matrix components. Accordingly, the chemical milieu and physical forces experienced by cells within a 3D tissue are fundamentally different than those experienced by cells grown in monolayer culture. This has been shown to markedly impact cellular morphology and signaling. Several methods have been devised to generate 3D cell cultures including encapsulation of cells in collagen gels or in biomaterial scaffolds. Such methods, while useful, do not recapitulate the intimate direct cell-cell adhesion architecture found in normal tissues. Rather, they more closely approximate culture systems in which single cells are loosely dispersed within a 3D meshwork of ECM products. Here, we describe a simple method in which cells are placed in hanging drop culture and incubated under physiological conditions until they form true 3D spheroids in which cells are in direct contact with each other and with extracellular matrix components. The method requires no specialized equipment and can be adapted to include addition of any biological agent in very small quantities that may be of interest in elucidating effects on cell-cell or cell-ECM interaction. The method can also be used to co-culture two (or more) different cell populations so as to elucidate the role of cell-cell or cell-ECM interactions in specifying spatial relationships between cells. Cell-cell cohesion and cell-ECM adhesion are the cornerstones of studies of embryonic development, tumor-stromal cell interaction in malignant invasion, wound healing, and for applications to tissue engineering. This simple method will provide a means of generating tissue-like cellular aggregates for measurement of biomechanical properties or for molecular and biochemical analysis in a physiologically relevant model.
Topics: Cell Adhesion; Cell Communication; Cell Culture Techniques; Extracellular Matrix; Spheroids, Cellular
PubMed: 21587162
DOI: 10.3791/2720 -
Developmental Biology May 2015
Topics: Cell Adhesion; Embryonic Development
PubMed: 25882001
DOI: 10.1016/j.ydbio.2015.02.015 -
Annual Review of Cell and Developmental... Oct 2022Since the proposal of the differential adhesion hypothesis, scientists have been fascinated by how cell adhesion mediates cellular self-organization to form spatial... (Review)
Review
Since the proposal of the differential adhesion hypothesis, scientists have been fascinated by how cell adhesion mediates cellular self-organization to form spatial patterns during development. The search for molecular tool kits with homophilic binding specificity resulted in a diverse repertoire of adhesion molecules. Recent understanding of the dominant role of cortical tension over adhesion binding redirects the focus of differential adhesion studies to the signaling function of adhesion proteins to regulate actomyosin contractility. The broader framework of differential interfacial tension encompasses both adhesion and nonadhesion molecules, sharing the common function of modulating interfacial tension during cell sorting to generate diverse tissue patterns. Robust adhesion-based patterning requires close coordination between morphogen signaling, cell fate decisions, and changes in adhesion. Current advances in bridging theoretical and experimental approaches present exciting opportunities to understand molecular, cellular, and tissue dynamics during adhesion-based tissue patterning across multiple time and length scales.
Topics: Actin Cytoskeleton; Actomyosin; Cell Adhesion
PubMed: 35562853
DOI: 10.1146/annurev-cellbio-120420-100215 -
Cell Adhesion & Migration 2008
Topics: Animals; Cell Adhesion; Cell Movement
PubMed: 19262104
DOI: 10.4161/cam.2.2.6518 -
Cold Spring Harbor Perspectives in... Aug 2018Cell adhesion systems are defined by their ability to resist detachment force. Our understanding of the biology of cell-cell adhesions has recently been transformed by... (Review)
Review
Cell adhesion systems are defined by their ability to resist detachment force. Our understanding of the biology of cell-cell adhesions has recently been transformed by the realization that many of the forces that act on those adhesions are generated by the cells that they couple together; and that force at adhesive junctions can be sensed to regulate cell behavior. Here, we consider the mechanisms responsible for applying force to cell-cell junctions and the mechanosensory pathways that detect those forces. We focus on cadherins, as these are the best-studied examples to date, but it is likely that similar principles will apply to other molecular systems that can engage with force-generators within cells and physically couple those cells together.
Topics: Animals; Cell Adhesion; Humans; Intercellular Junctions; Mechanotransduction, Cellular
PubMed: 28778874
DOI: 10.1101/cshperspect.a028761 -
Philosophical Transactions of the Royal... Aug 2019Cell division, the purpose of which is to enable cell replication, and in particular to distribute complete, accurate copies of genetic material to daughter cells, is... (Review)
Review
Cell division, the purpose of which is to enable cell replication, and in particular to distribute complete, accurate copies of genetic material to daughter cells, is essential for the propagation of life. At a morphological level, division not only necessitates duplication of cellular structures, but it also relies on polar segregation of this material followed by physical scission of the parent cell. For these fundamental changes in cell shape and positioning to be achieved, mechanisms are required to link the cell cycle to the modulation of cytoarchitecture. Outside of mitosis, the three main cytoskeletal networks not only endow cells with a physical cytoplasmic skeleton, but they also provide a mechanism for spatio-temporal sensing via integrin-associated adhesion complexes and site-directed delivery of cargoes. During mitosis, some interphase functions are retained, but the architecture of the cytoskeleton changes dramatically, and there is a need to generate a mitotic spindle for chromosome segregation. An economical solution is to re-use existing cytoskeletal molecules: transcellular actin stress fibres remodel to create a rigid cortex and a cytokinetic furrow, while unipolar radial microtubules become the primary components of the bipolar spindle. This remodelling implies the existence of specific mechanisms that link the cell-cycle machinery to the control of adhesion and the cytoskeleton. In this article, we review the intimate three-way connection between microenvironmental sensing, adhesion signalling and cell proliferation, particularly in the contexts of normal growth control and aberrant tumour progression. As the morphological changes that occur during mitosis are ancient, the mechanisms linking the cell cycle to the cytoskeleton/adhesion signalling network are likely to be primordial in nature and we discuss recent advances that have elucidated elements of this link. A particular focus is the connection between CDK1 and cell adhesion. This article is part of a discussion meeting issue 'Forces in cancer: interdisciplinary approaches in tumour mechanobiology'.
Topics: Cell Adhesion; Cell Cycle; Cell Proliferation; Cytoskeleton; Humans; Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 31431178
DOI: 10.1098/rstb.2018.0227 -
Current Opinion in Cell Biology Apr 2020Integrins are heterodimeric transmembrane receptors that connect the extracellular matrix environment to the actin cytoskeleton via adaptor molecules through assembly of... (Review)
Review
Integrins are heterodimeric transmembrane receptors that connect the extracellular matrix environment to the actin cytoskeleton via adaptor molecules through assembly of a range of adhesion structures. Recent advances in biochemical, imaging and biophysical methods have enabled a deeper understanding of integrin signalling and their associated regulatory processes. The identification of the consensus integrin-based 'adhesomes' within the last 5 years has defined common core components of adhesion complexes and associated partners. These approaches have also uncovered unexpected adhesion protein behaviour and molecules recruited to adhesion sites that have expanded our understanding of the molecular and physical control of integrin signalling.
Topics: Cell Adhesion; Cytoskeleton; Humans; Integrins
PubMed: 31945690
DOI: 10.1016/j.ceb.2019.12.008 -
Frontiers in Immunology 2019Cell-cell interactions and cell adhesion are key mediators of cancer progression and facilitate hallmarks of cancer including immune evasion and metastatic... (Review)
Review
Cell-cell interactions and cell adhesion are key mediators of cancer progression and facilitate hallmarks of cancer including immune evasion and metastatic dissemination. Many cell adhesion molecules within the tumor microenvironment are changed and significant alterations of glycosylation are observed. These changes in cell adhesion molecules alter the ability of tumor cells to interact with other cells and extracellular matrix proteins. Three families of cell-cell interaction molecules selectins, Siglecs, and integrins have been associated with cancer progression in many pre-clinical studies, yet inhibition of cell adhesion as a therapeutic target is just beginning to be explored. We review how cell-cell interactions mediated by integrins and the glycan-binding receptors selectins and Siglec receptors support cancer progression. The discussion focuses on mechanisms during immune evasion and metastasis that can be therapeutically targeted by blocking these cell-cell interactions.
Topics: Animals; Cell Adhesion; Cell Adhesion Molecules; Glycosylation; Humans; Immune Tolerance; Neoplasm Metastasis; Neoplasms; Signal Transduction; Tumor Microenvironment
PubMed: 31552050
DOI: 10.3389/fimmu.2019.02120 -
F1000Research 2018The epithelial lateral membrane plays a central role in the integration of intercellular signals and, by doing so, is a principal determinant in the emerging properties... (Review)
Review
The epithelial lateral membrane plays a central role in the integration of intercellular signals and, by doing so, is a principal determinant in the emerging properties of epithelial tissues. Mechanical force, when applied to the lateral cell-cell interface, can modulate the strength of adhesion and influence intercellular dynamics. Yet the relationship between mechanical force and epithelial cell behavior is complex and not completely understood. This commentary aims to provide an investigative look at the usage of cellular forces at the epithelial cell-cell adhesion interface.
Topics: Animals; Biomechanical Phenomena; Cell Adhesion; Cell Surface Extensions; Epithelial Cells; Epithelium; Humans; Muscle Contraction
PubMed: 30345009
DOI: 10.12688/f1000research.15860.1