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Cell Metabolism Jul 2021Altered tissue mechanics and metabolism are defining characteristics of cancer that impact not only proliferation but also migration. While migrating through a... (Review)
Review
Altered tissue mechanics and metabolism are defining characteristics of cancer that impact not only proliferation but also migration. While migrating through a mechanically and spatially heterogeneous microenvironment, changes in metabolism allow cells to dynamically tune energy generation and bioenergetics in response to fluctuating energy needs. Physical cues from the extracellular matrix influence mechanosignaling pathways, cell mechanics, and cytoskeletal architecture to alter presentation and function of metabolic enzymes. In cancer, altered mechanosensing and metabolic reprogramming supports metabolic plasticity and high energy production while cells migrate and metastasize. Here, we discuss the role of mechanoresponsive metabolism in regulating cell migration and supporting metastasis as well as the potential of therapeutically targeting cancer metabolism to block motility and potentially metastasis.
Topics: Animals; Cell Movement; Energy Metabolism; Extracellular Matrix; Humans; Mechanotransduction, Cellular; Neoplasm Metastasis; Neoplasms; Tumor Microenvironment
PubMed: 33915111
DOI: 10.1016/j.cmet.2021.04.002 -
Comprehensive Physiology Oct 2012Cell migration is fundamental to establishing and maintaining the proper organization of multicellular organisms. Morphogenesis can be viewed as a consequence, in part,... (Review)
Review
Cell migration is fundamental to establishing and maintaining the proper organization of multicellular organisms. Morphogenesis can be viewed as a consequence, in part, of cell locomotion, from large-scale migrations of epithelial sheets during gastrulation, to the movement of individual cells during development of the nervous system. In an adult organism, cell migration is essential for proper immune response, wound repair, and tissue homeostasis, while aberrant cell migration is found in various pathologies. Indeed, as our knowledge of migration increases, we can look forward to, for example, abating the spread of highly malignant cancer cells, retarding the invasion of white cells in the inflammatory process, or enhancing the healing of wounds. This article is organized in two main sections. The first section is devoted to the single-cell migrating in isolation such as occurs when leukocytes migrate during the immune response or when fibroblasts squeeze through connective tissue. The second section is devoted to cells collectively migrating as part of multicellular clusters or sheets. This second type of migration is prevalent in development, wound healing, and in some forms of cancer metastasis.
Topics: Animals; Cell Adhesion; Cell Movement; Chemotaxis, Leukocyte; Fibroblasts; Gap Junctions; Humans; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Tight Junctions; Wound Healing
PubMed: 23720251
DOI: 10.1002/cphy.c110012 -
Methods in Molecular Biology (Clifton,... 2023Cell migration and invasion have essential roles in both normal physiology and disease. As such, methodologies to assess cell migratory and invasive capacities are...
Cell migration and invasion have essential roles in both normal physiology and disease. As such, methodologies to assess cell migratory and invasive capacities are necessary to elucidate normal cell processes and underlying mechanisms of disease. Here, we describe commonly used transwell in vitro methods for the study of cell migration and invasion. The transwell migration assay involves the chemotaxis of cells through a porous membrane after the establishment of a chemoattractant gradient using two medium-filled compartments. The transwell invasion assay involves the addition of an extracellular matrix on top of the porous membrane which only permits chemotaxis of cells which possess invasive properties such as tumor cells.
Topics: Humans; Cell Movement; Chemotaxis; Neoplasm Invasiveness; Cell Migration Assays; Cell Line, Tumor
PubMed: 37142933
DOI: 10.1007/978-1-0716-3052-5_22 -
Nature Reviews. Molecular Cell Biology Aug 2021Cells have the ability to respond to various types of environmental cues, and in many cases these cues induce directed cell migration towards or away from these signals.... (Review)
Review
Cells have the ability to respond to various types of environmental cues, and in many cases these cues induce directed cell migration towards or away from these signals. How cells sense these cues and how they transmit that information to the cytoskeletal machinery governing cell translocation is one of the oldest and most challenging problems in biology. Chemotaxis, or migration towards diffusible chemical cues, has been studied for more than a century, but information is just now beginning to emerge about how cells respond to other cues, such as substrate-associated cues during haptotaxis (chemical cues on the surface), durotaxis (mechanical substrate compliance) and topotaxis (geometric features of substrate). Here we propose four common principles, or pillars, that underlie all forms of directed migration. First, a signal must be generated, a process that in physiological environments is much more nuanced than early studies suggested. Second, the signal must be sensed, sometimes by cell surface receptors, but also in ways that are not entirely clear, such as in the case of mechanical cues. Third, the signal has to be transmitted from the sensing modules to the machinery that executes the actual movement, a step that often requires amplification. Fourth, the signal has to be converted into the application of asymmetric force relative to the substrate, which involves mostly the cytoskeleton, but perhaps other players as well. Use of these four pillars has allowed us to compare some of the similarities between different types of directed migration, but also to highlight the remarkable diversity in the mechanisms that cells use to respond to different cues provided by their environment.
Topics: Animals; Cell Movement; Cell Polarity; Chemotaxis; Cytoskeleton; Humans; Signal Transduction
PubMed: 33990789
DOI: 10.1038/s41580-021-00366-6 -
Journal of Visualized Experiments : JoVE Jun 2014Migration is a key property of live cells and critical for normal development, immune response, and disease processes such as cancer metastasis and inflammation. Methods...
Migration is a key property of live cells and critical for normal development, immune response, and disease processes such as cancer metastasis and inflammation. Methods to examine cell migration are very useful and important for a wide range of biomedical research such as cancer biology, immunology, vascular biology, cell biology and developmental biology. Here we use tumor cell migration and invasion as an example and describe two related assays to illustrate the commonly used, easily accessible methods to measure these processes. The first method is the cell culture wound closure assay in which a scratch is generated on a confluent cell monolayer. The speed of wound closure and cell migration can be quantified by taking snapshot pictures with a regular inverted microscope at several time intervals. More detailed cell migratory behavior can be documented using the time-lapse microscopy system. The second method described in this paper is the transwell cell migration and invasion assay that measures the capacity of cell motility and invasiveness toward a chemo-attractant gradient. It is our goal to describe these methods in a highly accessible manner so that the procedures can be successfully performed in research laboratories even just with basic cell biology setup.
Topics: Animals; Cell Movement; Chemotaxis; Cytological Techniques; Melanoma, Experimental; Mice; NIH 3T3 Cells; Neoplasm Invasiveness
PubMed: 24962652
DOI: 10.3791/51046 -
Journal of Visualized Experiments : JoVE Mar 2018The aim of this work is to show a novel method to evaluate the ability of some immunomodulatory molecules, such as antimicrobial peptides (AMPs), to stimulate cell...
The aim of this work is to show a novel method to evaluate the ability of some immunomodulatory molecules, such as antimicrobial peptides (AMPs), to stimulate cell migration. Importantly, cell migration is a rate-limiting event during the wound-healing process to re-establish the integrity and normal function of tissue layers after injury. The advantage of this method over the classical assay, which is based on a manually made scratch in a cell monolayer, is the usage of special silicone culture inserts providing two compartments to create a cell-free pseudo-wound field with a well-defined width (500 μm). In addition, due to an automated image analysis platform, it is possible to rapidly obtain quantitative data on the speed of wound closure and cell migration. More precisely, the effect of two frog-skin AMPs on the migration of bronchial epithelial cells will be shown. Furthermore, pretreatment of these cells with specific inhibitors will provide information on the molecular mechanisms underlying such events.
Topics: Animals; Biological Assay; Cell Movement; Humans; Wound Healing
PubMed: 29608162
DOI: 10.3791/56825 -
British Journal of Pharmacology Dec 2014Cell movement is a fundamental process of normal cellular physiology and pathophysiology. Abnormal regulation of cell migration is a common denominator of many medical...
UNLABELLED
Cell movement is a fundamental process of normal cellular physiology and pathophysiology. Abnormal regulation of cell migration is a common denominator of many medical disorders, including cancer metastasis, autoimmune disease and inflammation. Increased interest in the targeting of cell migration and invasion, which has potential for therapeutic intervention in many diseases are behind this special themed issue. Thus, the focus of this issue is centred on the control of cellular cytoskeletal dynamics and cellular or tissue microenvironment sensors. Novel therapeutic opportunities targeting regulation of cell migration are discussed including the emerging roles of tetraspanins, phosphoinositides, transient receptor potential cation channels, stromal interaction molecules and calcium release-activated calcium modulators. Better understanding of these regulatory factors will hopefully bring greater attention to strategically targeting aberrant cell migration, which has many therapeutic implications for common human diseases.
LINKED ARTICLES
This article is part of a themed section on Cytoskeleton, Extracellular Matrix, Cell Migration, Wound Healing and Related Topics. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-24
Topics: Autoimmune Diseases; Cell Movement; Cytoskeleton; Humans; Inflammation; Neoplasm Invasiveness; Neoplasm Metastasis
PubMed: 25442220
DOI: 10.1111/bph.12849 -
International Journal of Molecular... Oct 2017Increasing evidence suggests that the water/glycerol channel aquaporin-3 (AQP3) plays a pivotal role in cancer metastasis. AQP3 knockout mice were resistant to skin... (Review)
Review
Increasing evidence suggests that the water/glycerol channel aquaporin-3 (AQP3) plays a pivotal role in cancer metastasis. AQP3 knockout mice were resistant to skin tumor formation and overexpression correlated with metastasis and poor prognosis in patients with breast or gastric cancer. In cultured cancer cells, increased AQP3 expression stimulated several intracellular signaling pathways and resulted in increased cell proliferation, migration, and invasion as well as aggravation of epithelial-to-mesenchymal transition. Besides AQP facilitated water transport at the leading edge of migrating cells, AQP3 signaling mechanisms are beginning to be unraveled. Here, we give a thorough review of current knowledge regarding AQP3 expression in cancer and how AQP3 contributes to cancer progression via signaling that modulates cellular mechanisms. This review article will expand our understanding of the known pathophysiological findings regarding AQP3 in cancer.
Topics: Animals; Aquaporin 3; Cell Movement; Cell Proliferation; Epithelial-Mesenchymal Transition; Humans
PubMed: 28991174
DOI: 10.3390/ijms18102106 -
Frontiers in Immunology 2022
Topics: Cell Movement; Immune System Phenomena
PubMed: 35493502
DOI: 10.3389/fimmu.2022.897626 -
Frontiers in Immunology 2022
Topics: Cytoskeleton; Cell Movement; Microtubules
PubMed: 36311712
DOI: 10.3389/fimmu.2022.1057533