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Amoeboid mesenchymal

Meng Sun, Muhammad H Zaman
Cell migration is a complex and multistep process involved in homeostasis maintenance, morphogenesis, and disease development, such as cancer metastasis. Modeling cell migration and the relevant cytoskeleton dynamics have profound implications for studying fundamental development and disease diagnosis. This review focuses on some recent models of both cell migration and migration-related cytoskeleton dynamics, addressing issues such as the difference between amoeboid and mesenchymal migration modes, and between single-cell migration and collective cell migration...
November 15, 2016: Wiley Interdisciplinary Reviews. Systems Biology and Medicine
Atsuko Hara, Miki Hashimura, Koji Tsutsumi, Masashi Akiya, Madoka Inukai, Yasutaka Ohta, Makoto Saegusa
FilGAP, a Rac-specific Rho-GTPase-activating protein (GAP), acts as a mediator of Rho/ROCK-dependent amoeboid movement, and its knockdown results in Rac-driven mesenchymal morphology. Herein, we focused on the possible roles of FilGAP expression in astrocytomas. In clinical samples, FilGAP expression was significantly increased in grade (G) II astrocytomas as compared to normal astrocytes, but its expression strongly decreased in a grade-dependent manner, and was positively associated with isocitrate dehydrogenase 1 (IDH1) mutations and inversely to cytoplasmic Rac1...
October 27, 2016: Cancer Medicine
Haruka Handa, Ari Hashimoto, Shigeru Hashimoto, Hisataka Sabe
Modes of cancer invasion interchange between the mesenchymal type and amoeboid type in response to the microenvironment, in which RhoA and Rac1 are selectively required to perform different modes of actin-cytoskeletal remodeling. Membrane remodeling is another integral part of invasion. Arf6 regulates the recycling of molecules at the cell periphery, and is often overexpressed in malignant cancers together with its effector AMAP1/ASAP1/DDEF1. This pathway promotes mesenchymal-type invasion when AMAP1 binds to EPB41L5, a mesenchymal-specific protein induced by ZEB1...
October 18, 2016: Small GTPases
Jie Zhu, Alex Mogilner
Cell migration on a two-dimensional flat surface has been extensively studied and is generally characterized by a front-protrusion-rear-contraction process. In a three-dimensional (3D) environment, on the other hand, cells adopt multiple migration strategies depending on the cell type and the properties of the extracellular matrix (ECM). By using computer simulations, we find that these migration strategies can be classified by various spatial-temporal dynamics of actin protrusion, actin-myosin contraction and actin-ECM adhesion...
October 6, 2016: Interface Focus
Jonathan Bergeman, Alexia Caillier, François Houle, Laurence M Gagné, Marc-Étienne Huot
By progressing through the epithelial to mesenchymal transition (EMT), cancer cells gain the ability to leave the primary tumor site and invade surrounding tissues. These metastatic cancers cells can further increase their plasticity by adopting an amoeboid-like morphology, by undergoing mesenchymal to amoeboid transition (MAT). We found that adhering cells producing spreading initiation centers (SIC), a transient structure localized above nascent adhesion complexes, share common biological and morphological characteristics associated with amoeboid cells...
September 16, 2016: Journal of Cell Science
Jaakko Lehtimäki, Markku Hakala, Pekka Lappalainen
Cell migration is necessary for several developmental processes in multicellular organisms. Furthermore, many physiological processes such as wound healing and immunological events in adult animals are dependent on cell migration. Consequently, defects in cell migration are linked to various diseases including immunological disorders as well as cancer progression and metastasis formation. Cell migration is driven by specific protrusive and contractile actin filament structures, but the types and relative contributions of these actin filament arrays vary depending on the cell type and the environment of the cell...
July 29, 2016: Handbook of Experimental Pharmacology
Guillermo Ramírez-Santiago, Javier Robles-Valero, Giulia Morlino, Aranzazu Cruz-Adalia, Manuel Pérez-Martínez, Airen Zaldivar, Mónica Torres-Torresano, Francisco Javier Chichón, Andrea Sorrentino, Eva Pereiro, José L Carrascosa, Diego Megías, Carlos Oscar S Sorzano, Francisco Sánchez-Madrid, Esteban Veiga
Lymphocyte migration, which is essential for effective immune responses, belongs to the so-called amoeboid migration. The lymphocyte migration is up to 100 times faster than between mesenchymal and epithelial cell types. Migrating lymphocytes are highly polarized in three well-defined structural and functional zones: uropod, medial zone, and leading edge (LE). The actiomyosin-dependent driving force moves forward the uropod, whereas massive actin rearrangements protruding the cell membrane are observed at the LE...
October 2016: European Journal of Immunology
Eliah R Shamir, Kester Coutinho, Dan Georgess, Manfred Auer, Andrew J Ewald
Dissemination is the process by which cells detach and migrate away from a multicellular tissue. The epithelial-to-mesenchymal transition (EMT) conceptualizes dissemination in a stepwise fashion, with downregulation of E-cadherin leading to loss of intercellular junctions, induction of motility, and then escape from the epithelium. This gain of migratory activity is proposed to be mutually exclusive with proliferation. We previously developed a dissemination assay based on inducible expression of the transcription factor Twist1 and here utilize it to characterize the timing and dynamics of intercellular adhesion, proliferation and migration during dissemination...
September 15, 2016: Biology Open
Cristina Belgiovine, Giulio Chiesa, Ilaria Chiodi, Roberta Frapolli, Katiuscia Bonezzi, Giulia Taraboletti, Maurizio D'Incalci, Chiara Mondello
Cancer cells use two major types of movement: Mesenchymal, which is typical of cells of mesenchymal origin and depends on matrix metalloproteinase (MMP) activity, and amoeboid, which is characteristic of cells with a rounded shape and relies on the activity of Rho-associated kinase (ROCK). The present authors previously demonstrated that, during neoplastic transformation, telomerase-immortalized human fibroblasts (cen3tel cells) acquired a ROCK-dependent/MMP independent mechanism of invasion, mediated by the downregulation of the ROCK cellular inhibitor Round (Rnd)3/RhoE...
July 2016: Oncology Letters
Maryna Kapustina, Denis Tsygankov, Jia Zhao, Timothy Wessler, Xiaofeng Yang, Alex Chen, Nathan Roach, Timothy C Elston, Qi Wang, Ken Jacobson, M Gregory Forest
Cells transition from spread to rounded morphologies in diverse physiological contexts including mitosis and mesenchymal-to-amoeboid transitions. When these drastic shape changes occur rapidly, cell volume and surface area are approximately conserved. Consequently, the rounded cells are suddenly presented with a several-fold excess of cell surface whose area far exceeds that of a smooth sphere enclosing the cell volume. This excess is stored in a population of bleb-like protrusions (BLiPs), whose size distribution is shown by electron micrographs to be skewed...
March 2016: PLoS Computational Biology
Annika Weigand, Anja M Boos, Kereshmeh Tasbihi, Justus P Beier, Paul D Dalton, Michael Schrauder, Raymund E Horch, Matthias W Beckmann, Pamela L Strissel, Reiner Strick
BACKGROUND: There is a need to establish more cell lines from breast tumors in contrast to immortalized cell lines from metastatic effusions in order to represent the primary tumor and not principally metastatic biology of breast cancer. This investigation describes the simultaneous isolation, characterization, growth and function of primary mammary epithelial cells (MEC), mesenchymal cells (MES) and adipose derived stem cells (ADSC) from four normal breasts, one inflammatory and one triple-negative ductal breast tumors...
2016: Breast Cancer Research: BCR
Aneta Gandalovičová, Tomáš Vomastek, Daniel Rosel, Jan Brábek
Apico-basal polarity is typical of cells present in differentiated epithelium while front-rear polarity develops in motile cells. In cancer development, the transition from epithelial to migratory polarity may be seen as the hallmark of cancer progression to an invasive and metastatic disease. Despite the morphological and functional dissimilarity, both epithelial and migratory polarity are controlled by a common set of polarity complexes Par, Scribble and Crumbs, phosphoinositides, and small Rho GTPases Rac, Rho and Cdc42...
May 3, 2016: Oncotarget
Jessica Konen, Scott Wilkinson, Byoungkoo Lee, Haian Fu, Wei Zhou, Yi Jiang, Adam I Marcus
LKB1 is a serine/threonine kinase and a commonly mutated gene in lung adenocarcinoma. The majority of LKB1 mutations are truncations that disrupt its kinase activity and remove its C-terminal domain (CTD). Because LKB1 inactivation drives cancer metastasis in mice and leads to aberrant cell invasion in vitro, we sought to determine how compromised LKB1 function affects lung cancer cell polarity and invasion. Using three-dimensional models, we show that LKB1 kinase activity is essential for focal adhesion kinase-mediated cell adhesion and subsequent collagen remodeling but not cell polarity...
April 1, 2016: Molecular Biology of the Cell
Andrew C Callan-Jones, Raphaël Voituriez
Eukaryotic cell movement is characterized by very diverse migration modes. Recent studies show that cells can adapt to environmental cues, such as adhesion and geometric confinement, thereby readily switching their mode of migration. Among this diversity of motile behavior, actin flows have emerged as a highly conserved feature of both mesenchymal and amoeboid migration, and have also been identified as key regulators of cell polarity. This suggests that the various observed migration modes are continuous variations of elementary locomotion mechanisms, based on a very robust physical property of the actin/myosin system - its ability to sustain flows at the cell scale...
February 2016: Current Opinion in Cell Biology
Bin Huang, Mohit Kumar Jolly, Mingyang Lu, Ilan Tsarfaty, Eshel Ben-Jacob, Jose' N Onuchic
Cellular plasticity during cancer metastasis is a major clinical challenge. Two key cellular plasticity mechanisms -Epithelial-to-Mesenchymal Transition (EMT) and Mesenchymal-to-Amoeboid Transition (MAT) - have been carefully investigated individually, yet a comprehensive understanding of their interconnections remains elusive. Previously, we have modeled the dynamics of the core regulatory circuits for both EMT (miR-200/ZEB/miR-34/SNAIL) and MAT (Rac1/RhoA). We now extend our previous work to study the coupling between these two core circuits by considering the two microRNAs (miR-200 and miR-34) as external signals to the core MAT circuit...
2015: Scientific Reports
Matthew P Caley, Helen King, Neel Shah, Kai Wang, Mercedes Rodriguez-Teja, Julian H Gronau, Jonathan Waxman, Justin Sturge
The diverse composition and structure of extracellular matrix (ECM) interfaces encountered by tumor cells at secondary tissue sites can influence metastatic progression. Extensive in vitro and in vivo data has confirmed that metastasizing tumor cells can adopt different migratory modes in response to their microenvironment. Here we present a model that uses human stromal cell-derived matrices to demonstrate that plasticity in tumor cell movement is controlled by the tumor-associated collagen receptor Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) and the crosslinking of collagen fibers by stromal-derived lysyl oxidase (LOX)...
February 2016: Clinical & Experimental Metastasis
Gaia Cantelli, Jose L Orgaz, Irene Rodriguez-Hernandez, Panagiotis Karagiannis, Oscar Maiques, Xavier Matias-Guiu, Frank O Nestle, Rosa M Marti, Sophia N Karagiannis, Victoria Sanz-Moreno
Cell migration underlies metastatic dissemination of cancer cells, and fast "amoeboid" migration in the invasive fronts of tumors is controlled by high levels of actomyosin contractility. How amoeboid migration is regulated by extracellular signals and sustained over time by transcriptional changes is not fully understood. Transforming growth factor β (TGF-β) is well known to promote epithelial-to-mesenchymal transition (EMT) and contribute to metastasis, but melanocytes are neural crest derivatives that have undergone EMT during embryonic development...
November 16, 2015: Current Biology: CB
Alanna E Sedgwick, James W Clancy, M Olivia Balmert, Crislyn D'Souza-Schorey
Tumor cell invasion requires the molecular and physical adaptation of both the cell and its microenvironment. Here we show that tumor cells are able to switch between the use of microvesicles and invadopodia to facilitate invasion through the extracellular matrix. Invadopodia formation accompanies the mesenchymal mode of migration on firm matrices and is facilitated by Rac1 activation. On the other hand, during invasion through compliant and deformable environments, tumor cells adopt an amoeboid phenotype and release microvesicles...
October 13, 2015: Scientific Reports
Wei Yang, Chunxiong Luo, Luhua Lai, Qi Ouyang
The cell's micro-environment plays an important role in various physiological and pathological phenomena. To better investigate in vivo cellular behaviors, researchers have expended great effort in building controlled in vitro biophysical and biochemical environments. Because a cell's gaseous environment affects properties such as its division, metastasis, and differentiation, we developed a zero-flow based platform for studying mammalian cell chemotaxis behavior in different oxygen environments. This platform can construct a linear range of oxygen tensions within one chip (i...
July 2015: Biomicrofluidics
Sam Cooper, Amine Sadok, Vicky Bousgouni, Chris Bakal
Melanoma cells can adopt two functionally distinct forms, amoeboid and mesenchymal, which facilitates their ability to invade and colonize diverse environments during the metastatic process. Using quantitative imaging of single living tumor cells invading three-dimensional collagen matrices, in tandem with unsupervised computational analysis, we found that melanoma cells can switch between amoeboid and mesenchymal forms via two different routes in shape space--an apolar and polar route. We show that whereas particular Rho-family GTPases are required for the morphogenesis of amoeboid and mesenchymal forms, others are required for transitions via the apolar or polar route and not amoeboid or mesenchymal morphogenesis per se...
November 5, 2015: Molecular Biology of the Cell
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