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| Open AccessNon-catalytic role of phosphoinositide 3-kinase in mesenchymal cell migration through non-canonical induction of p85β/AP2-mediated endocytosis
PI3 kinase is known to promote cell migration through its catalytic activity. Here, the authors show that the kinase also induces endocytosis through a non-catalytic pathway that actually decreases migratory speed and persistence, revealing a more subtle regulation of motility.
- Hideaki T. Matsubayashi
- , Jack Mountain
- & Takanari Inoue
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Article
| Open AccessFocal adhesions contain three specialized actin nanoscale layers
Focal adhesions are dynamic structures that link the cell to the extracellular matrix. Here, the authors report that focal adhesions contain tropomyosin-decorated actin filaments, and show evidence that suggests specific functions in adhesion dynamics and cell migration.
- Reena Kumari
- , Katharina Ven
- & Pekka Lappalainen
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| Open AccessMitochondrial metabolism sustains CD8+ T cell migration for an efficient infiltration into solid tumors
The migration of T cells into tumours and how this is regulated by metabolic pathways is not completely understood. Here the authors use human and xenograft mouse models to explore the functional changes in T cells during migration in tumours and how glycolytic and TCA cycle metabolism is involved.
- Luca Simula
- , Mattia Fumagalli
- & Emmanuel Donnadieu
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Article
| Open AccessCanonical and non-canonical integrin-based adhesions dynamically interconvert
Cells employ integrin-based adhesions with different molecular compositions to adhere to substrates. Here, the authors show that so-called “non-canonical” adhesions lacking focal adhesion components can convert to focal adhesions (and vice versa), through the selective exchange of components.
- Fabian Lukas
- , Claudia Matthaeus
- & Tanja Maritzen
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Article
| Open AccessIntercellular transfer of cancer cell invasiveness via endosome-mediated protease shedding
The matrix metalloprotease MT1-MMP drives cancer metastasis. Here, the authors demonstrate how invasive cancer cells instigate non-invasive neighbouring cells to become degradative and invasive by transferring catalytically active MT1-MMP fragments.
- Eva Maria Wenzel
- , Nina Marie Pedersen
- & Camilla Raiborg
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Article
| Open AccessMotility and tumor infiltration are key aspects of invariant natural killer T cell anti-tumor function
Invariant natural killer T (iNKT) cells are important contributors to anti-tumour immunity, but they often become dysfunctional in cancers. Here authors show that inhibited iNKT intra-tumour motility and iNKT cell exclusion from tumours by macrophages both contribute to their diminished function in cancer, and by therapeutic interference with the respective motility and iNKT-macrophage interaction pathways, their function can be restored.
- Chenxi Tian
- , Yu Wang
- & Li Bai
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Article
| Open AccessAndrogen drives melanoma invasiveness and metastatic spread by inducing tumorigenic fucosylation
Mechanisms underlying sex associated differences in the role of androgen receptor (AR) in melanoma are unclear. Here the authors show that androgen-activated AR transcriptionally upregulates fucosyltransferase 4, which fucosylates L1CAM and promotes melanoma invasiveness by disrupting adherens junctions.
- Qian Liu
- , Emma Adhikari
- & Eric K. Lau
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Article
| Open AccessEtrolizumab-s fails to control E-Cadherin-dependent co-stimulation of highly activated cytotoxic T cells
The clinical success of anti- αEβ7 antibody Etrolizumab for Crohn’s disease is less than what is expected based on proof-of-concept studies. Here authors show, by characterization of T cells from Etrolizumab-treated patients, in vitro functional assays and reanalysis of public single cell datasets on Etrolizumab-treated patients, that at high level of T cell activation, which characterises T cells in Crohn’s disease, E-Cadherin-αEβ7 interactions become resistant to Etrolizumab inhibition.
- Maximilian Wiendl
- , Mark Dedden
- & Sebastian Zundler
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Article
| Open AccessExpression of E-cadherin by CD8+ T cells promotes their invasion into biliary epithelial cells
The presence of CD8+ T cells in the cytoplasm of biliary epithelial cells (BEC) has been associated with primary biliary cholangitis. Here, the authors demonstrate that CD8+ T cells invade BEC using a mechanism that is dependent on cytoskeletal rearrangements and E-cadherin:β-catenin interactions.
- Scott P. Davies
- , Vincenzo Ronca
- & Ye H. Oo
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Article
| Open AccessSpatial structure, chemotaxis and quorum sensing shape bacterial biomass accumulation in complex porous media
Pores and channels within complex porous structures, such as the soil or the human gut, influence fluid flow and thus bacterial colonization. Here, Scheidweiler et al. study bacterial colonization of a model complex porous structure and show how the interactions between fluid flow, microscale structure, chemotaxis, and gradients of a quorum-sensing signaling molecule control the heterogenous accumulation of bacterial biomass.
- David Scheidweiler
- , Ankur Deep Bordoloi
- & Pietro de Anna
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Article
| Open AccessRho GTPase activity crosstalk mediated by Arhgef11 and Arhgef12 coordinates cell protrusion-retraction cycles
Cell movements are achieved by the spatio-temporal coordination of local membrane protrusions and retractions. Here, the authors identify a mechanism by which these protrusion and retraction events are coupled and how this affects the directionality of cell movements.
- Suchet Nanda
- , Abram Calderon
- & Leif Dehmelt
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Article
| Open AccessT cell migration requires ion and water influx to regulate actin polymerization
The ability of T cells to migrate is a central component of their functionality and is known to require WNK1 kinase that is linked to the influx of ions into the cell. Here the authors show that T cell migration requires WNK1 mediated ion and water influx to swell the membrane of the leading edge and support actin polymerisation and forward motility.
- Leonard L. de Boer
- , Lesley Vanes
- & Victor L. J. Tybulewicz
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Article
| Open AccessMyeloid cells interact with a subset of thyrocytes to promote their migration and follicle formation through NF-κB
The mechanism underlying thyroid follicle formation is not well understood. Here, the authors show that a subgroup of NF-κB-activated thyrocytes, through interactions with myeloid cells, exhibit increased migration capacity to generate new follicles.
- Yang Rui-Meng
- , Song Shi-Yang
- & Song Huai-Dong
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Article
| Open AccessCXCL12 targets the primary cilium cAMP/cGMP ratio to regulate cell polarity during migration
Regulation of cell polarity is key to ensure directed cell migration. Here, Atkins et al. identify the primary cilium cAMP/cGMP ratio as a master regulator of the cell polarity of migrating cortical interneurons downstream of the CXCL12 chemokine.
- Melody Atkins
- , Maud Wurmser
- & Christine Métin
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Article
| Open AccessA dynamic partitioning mechanism polarizes membrane protein distribution
Different membrane proteins dynamically polarize to organize signal transduction, but the underlying mechanism is unclear. Here, the authors show that a differential diffusion mediated partitioning process is sufficient to drive such spatiotemporal patterning of membrane-associated signaling proteins.
- Tatsat Banerjee
- , Satomi Matsuoka
- & Pablo A. Iglesias
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Article
| Open AccessFate specification is spatially intermingled across planarian stem cells
Stem cells can select among a wide array of fates. Here, the authors utilize spatial transcriptomics and three-dimensional neighborhood analysis to uncover that fate choices in planarian stem cells occur in a highly intermingled pattern.
- Chanyoung Park
- , Kwadwo E. Owusu-Boaitey
- & Peter W. Reddien
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Article
| Open AccessA circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stability
TGFbeta is known to promote cancer metastasis through the promotion of epithelial-mesenchymal transition (EMT). Here, the authors demonstrate that a TGFbeta induced circular RNA (circITGB6) promotes colorectal cancer metastasis via activation of the m6A reader protein, IGF2BP3, resulting in stabilization of an EMT-promoting gene, PDPN.
- Ke Li
- , Jiawei Guo
- & Yong Peng
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Article
| Open AccessLung extracellular matrix modulates KRT5+ basal cell activity in pulmonary fibrosis
Idiopathic pulmonary fibrosis has been associated with aberrant expansion of KRT5-expressing basal cells. Here the authors show how changes in the ECM glycoprotein SPARC restrict the movement of KRT5+ cells, affecting their retention within fibrotic tissue.
- Richard J. Hewitt
- , Franz Puttur
- & Clare M. Lloyd
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Article
| Open AccessYAP silencing by RB1 mutation is essential for small-cell lung cancer metastasis
Small cell lung cancers (SCLC) have often inactivating mutations in RB1. In this study, the authors demonstrate that RB1 loss mediates low expression of YAP1 in SCLC tumors ultimately promoting metastasis and they propose to use benzamide family HDAC inhibitors to induce YAP1 expression for prevention of metastases.
- Zhengming Wu
- , Junhui Su
- & Kun-Liang Guan
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Article
| Open AccessSRC and TKS5 mediated podosome formation in fibroblasts promotes extracellular matrix invasion and pulmonary fibrosis
The activation and accumulation of lung fibroblasts resulting in aberrant deposition of extracellular matrix components is a pathogenic hallmark of idiopathic pulmonary fibrosis. Here, the authors show that the formation of podosomes in lung fibroblasts stimulates extracellular matrix invasion in a mouse model of the disease, suggesting that pharmacological targeting of podosome formation or organization might be a therapeutic option.
- Ilianna Barbayianni
- , Paraskevi Kanellopoulou
- & Vassilis Aidinis
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Article
| Open AccessEpithelial plasticity and innate immune activation promote lung tissue remodeling following respiratory viral infection
After respiratory viral infection and in fibrotic lung disease, repair and remodeling processes particularly affect airway basal cell (BC) and alveolar epithelial cell populations. Here, using single cell transcriptomics and lineage tracing, the authors characterize this process and define roles for innate immune activation in the regulation of BC fate and alveolar remodeling.
- Andrew K. Beppu
- , Juanjuan Zhao
- & Barry R. Stripp
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Article
| Open AccessWhole-genome screens reveal regulators of differentiation state and context-dependent migration in human neutrophils
Neutrophils provide a critical early defense as part of our innate immune system. Here, authors performed a genome-wide assessment of the molecular factors critical to proliferation, differentiation, and cell migration in a neutrophil-like cell.
- Nathan M. Belliveau
- , Matthew J. Footer
- & Julie A. Theriot
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Article
| Open AccessSensing their plasma membrane curvature allows migrating cells to circumvent obstacles
Motile cells must navigate complex environments. Here the authors use state-of-the-art imaging, coarse-grained MD simulations and experimental biophysics to show that cells sense their plasma membrane curvature to circumvent obstacles.
- Ewa Sitarska
- , Silvia Dias Almeida
- & Alba Diz-Muñoz
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Article
| Open AccessCell diversity and plasticity during atrioventricular heart valve EMTs
Lotto et al. delineate cell diversity and mechanisms during heart valve development using scRNA-seq. They identify distinct cell types and states, the emergence of epithelial-mesenchymal plasticity, and cell interactions that may govern this process.
- Jeremy Lotto
- , Rebecca Cullum
- & Pamela A. Hoodless
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Article
| Open AccessSwitch of cell migration modes orchestrated by changes of three-dimensional lamellipodium structure and intracellular diffusion
How do cells regulate their migration speed and direction? Here, authors discover that keratocyte cells can reversibly switch between different migration modes, by changing the 3D lamellipodium shape and intracellular diffusion.
- Chao Jiang
- , Hong-Yu Luo
- & Hui Li
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Article
| Open AccessOntogenetically distinct neutrophils differ in function and transcriptional profile in zebrafish
Neutrophil ontogeny in zebrafish may be a continuum or consist of distinct lineages. Here the authors characterise neutrophils derived from rostral blood island and caudal haematopoietic tissue lineages and show differential gene expression and function in steady state and during wound healing.
- Juan P. García-López
- , Alexandre Grimaldi
- & Carmen G. Feijoo
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Article
| Open AccessA genetically encoded sensor for visualizing leukotriene B4 gradients in vivo
Leukotriene B4 (LTB4) is a potent lipid chemoattractant driving leukocyte migration and neutrophil swarming, but methods for its real-time detection are lacking. Here, the authors develop GEM-LTB4, a genetically encoded fluorescent biosensor, and use it to visualize leukocyte-derived LTB4 gradients.
- Szimonetta Xénia Tamás
- , Benoit Thomas Roux
- & Balázs Enyedi
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| Open AccessMolecular basis and design principles of switchable front-rear polarity and directional migration in Myxococcus xanthus
Cell polarity is key to many processes in bacteria. By focusing on the roadblock domain protein MglC, the authors elucidate the mechanistic basis and design principles of a system that spatiotemporally regulates switchable front-rear polarity and directional migration.
- Luís António Menezes Carreira
- , Dobromir Szadkowski
- & Lotte Søgaard-Andersen
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Article
| Open AccessInherited ARPC5 mutations cause an actinopathy impairing cell motility and disrupting cytokine signaling
Mutations that impact the function of the Arp2/3 complex are known to cause inborn errors of immunity. Here the authors describe biallelic null mutations in the ARPC5 subunit of Arp2/3 that disrupt actin function and cytokine signaling, causing infections, autoimmunity, inflammation and dysmorphisms.
- Cristiane J. Nunes-Santos
- , HyeSun Kuehn
- & Sergio D. Rosenzweig
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Article
| Open AccessPPP2R1A regulates migration persistence through the NHSL1-containing WAVE Shell Complex
The WAVE regulatory complex activates Arp2/3 at the cell cortex and in membrane protrusions to generate persistent cell migration. Here authors show that PPP2R1A, a scaffold subunit of protein phosphatase 2, associates with an alternative form of the WAVE complex where WAVE, the subunit that activates Arp2/3, is replaced by NHSL1.
- Yanan Wang
- , Giovanni Chiappetta
- & Alexis M. Gautreau
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Article
| Open AccessCNK2 promotes cancer cell motility by mediating ARF6 activation downstream of AXL signalling
Cancer cell motility is necessary for cell invasion and metastasis. Here, the authors identify CNK2 as a key mediator of cancer cell motility, linking extracellular stimuli via AXL signalling and downstream activation of ARF6 GTPase, resulting in increased metastasis in preclinical models.
- Guillaume Serwe
- , David Kachaner
- & Marc Therrien
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Article
| Open AccessWound infiltrating adipocytes are not myofibroblasts
Adipocyte plasticity during injury repair is debated. Here, the authors find that injury causes temporary adipocyte migration, but without lineage conversion to myofibroblasts. Distinct migration patterns, transcriptomics and ECM depositions indicate that adipocytes, unlike fibroblasts, do not contribute to fibrotic scars.
- Shruthi Kalgudde Gopal
- , Ruoxuan Dai
- & Yuval Rinkevich
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| Open AccessPlasmodium sporozoite search strategy to locate hotspots of blood vessel invasion
Plasmodium sporozoites actively migrate in the dermis and enter blood vessels to induce infection. Here, Formaglio et al. show that Plasmodium sporozoites alternate global superdiffusive skin exploration and local subdiffusive blood vessel exploitation to find intravasation hotspots associated with pericytes, enter the blood circulation and start malaria infection.
- Pauline Formaglio
- , Marina E. Wosniack
- & Rogerio Amino
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Article
| Open AccessAMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration
Cell metabolism must adapt to the energy needs of migrating cells. This study finds that fast amoeboid migrating cells harbor high AMPK activity, which controls both mitochondrial dynamics and cytoskeletal remodeling, enabling reduced energy needs.
- Eva Crosas-Molist
- , Vittoria Graziani
- & Victoria Sanz-Moreno
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Article
| Open AccessComputational design of dynamic receptor—peptide signaling complexes applied to chemotaxis
Engineering protein biosensors that respond to biomolecules by triggering cellular responses has largely relied on binding rigid molecules. Here, the authors develop a computational strategy for designing signaling complexes between conformationally dynamic proteins and peptides.
- Robert E. Jefferson
- , Aurélien Oggier
- & Patrick Barth
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Article
| Open AccessA Yap-dependent mechanoregulatory program sustains cell migration for embryo axis assembly
YAP signaling has been established as a mechanotransductive pathway in multiple contexts, but its developmental roles are still being explored. Here they show that YAP signaling sustains intracellular tension to direct cell migration during embryonic axis assembly.
- Ana Sousa-Ortega
- , Javier Vázquez-Marín
- & Juan R. Martínez-Morales
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Article
| Open AccessEndothelial deletion of PTBP1 disrupts ventricular chamber development
Alternative splicing crucially affects various biological processes, however, its function in heart development is largely unknown. Here, the authors show an essential role of alternative splicing factor PTBP1 in ventricular chamber development.
- Hongyu Liu
- , Ran Duan
- & Yi-Han Chen
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Article
| Open AccessYBX1 integration of oncogenic PI3K/mTOR signalling regulates the fitness of malignant epithelial cells
The understanding of molecular mechanisms in different subtypes of head and neck cancer (HNC) will define subtype-specific treatment options. Here the authors show that PI3K-phospho-YBX1 axis promotes tumour growth in basal subtype of HNC, while unphosphorylated YBX1 acts as a suppressor of metastasis in the mesenchymal subtype with inactive PI3K signalling.
- Yuchen Bai
- , Carolin Gotz
- & Charbel Darido
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Article
| Open AccessPIP4K2B is mechanoresponsive and controls heterochromatin-driven nuclear softening through UHRF1
PIP4Ks are phosphoinositide kinases often dysregulated in cancer. Here Poli and colleagues find that PIP4K2B is downregulated on soft substrates, and its depletion leads to altered nuclear mechanical properties and defects in cell spreading and motility.
- Alessandro Poli
- , Fabrizio A. Pennacchio
- & Paolo Maiuri
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Article
| Open AccessTetraspanin 4 stabilizes membrane swellings and facilitates their maturation into migrasomes
Migrasomes are signaling organelles that form in retraction fibers of migrating cells. Here authors show that migrasomes form by a two-stage process: an initial local membrane swelling matures and is stabilized by recruited tetraspanin proteins.
- Raviv Dharan
- , Yuwei Huang
- & Raya Sorkin
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Article
| Open AccessGenomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer
The intermediate states of the epithelial-to-mesenchymal transition (EMT) in cancer require further molecular characterisation. Here, the authors develop a method to evaluate EMT transformation and trajectories in cancer transcriptomics data, characterising EMT macro-states, including a hybrid state, and EMT hallmarks.
- Guidantonio Malagoli Tagliazucchi
- , Anna J. Wiecek
- & Maria Secrier
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Article
| Open AccessParallelized multidimensional analytic framework applied to mammary epithelial cells uncovers regulatory principles in EMT
Epithelial-to-mesenchymal transition (EMT) is a complex process regulated at multiple molecular levels. Here, the authors implement an analytic framework - PAMAF - to integrate data from twelve distinct omics modalities, which they use to understand the molecular changes and regulation during EMT in vitro.
- Indranil Paul
- , Dante Bolzan
- & Andrew Emili
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Article
| Open AccessSt18 specifies globus pallidus projection neuron identity in MGE lineage
The medial ganglionic eminence produces both interneurons and projection neurons, though how this fate choice is made is not well established. Here they show that St18 regulates migration and morphology of MGE neurons, inducing projection neuron fates.
- Luke F. Nunnelly
- , Melissa Campbell
- & Edmund Au
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Article
| Open AccessIntegration of single-cell transcriptomes and biological function reveals distinct behavioral patterns in bone marrow endothelium
Here Kim et al. show that primary BMECs can be maintained ex vivo as distinct sinusoidal- and arterial-like populations and that the presence of macrophages is critical to preserve their native transcriptomic profiles and functional heterogeneity.
- Young-Woong Kim
- , Greta Zara
- & Nadia Carlesso
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Article
| Open AccessFOXQ1 recruits the MLL complex to activate transcription of EMT and promote breast cancer metastasis
Forkhead box transcription factor, FOXQ1 is reported to promote epithelial-mesenchymal transition (EMT) and cancer metastasis. Here the authors show that FOXQ1 recruits the KMT2/MLL histone methyltransferase complex as a transcriptional coactivator to activate EMT programme in breast cancer.
- Allison V. Mitchell
- , Ling Wu
- & Guojun Wu
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Article
| Open AccessMulticiliated cells use filopodia to probe tissue mechanics during epithelial integration in vivo
Cell integration is a critical process in shaping complex tissues. Ventura and Amiri et al. reveal how multiciliated cells exert forces using filopodia to probe and remodel the neighboring cells, facilitating the formation of a susceptible environment for their integration in vivo.
- Guilherme Ventura
- , Aboutaleb Amiri
- & Jakub Sedzinski
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Article
| Open AccessPolarized NHE1 and SWELL1 regulate migration direction, efficiency and metastasis
Cell migration regulates diverse (patho)physiological processes, including cancer metastasis. Here the authors show that the chloride ion channel SWELL1 and the ion exchanger NHE1 are preferentially enriched at the trailing and leading edges, respectively, of migrating cells and regulate cell volume to propel confined cells, favouring breast cancer cell extravasation and metastasis.
- Yuqi Zhang
- , Yizeng Li
- & Konstantinos Konstantopoulos
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Article
| Open AccessCaldesmon controls stress fiber force-balance through dynamic cross-linking of myosin II and actin-tropomyosin filaments
In this study the authors report that Caldesmon controls force-balance and architecture of stress fibers through dynamic cross-linking of actin and myosin filaments. Caldesmon depletion led to consequent problems in cell morphogenesis, motility and mechanosensing.
- Shrikant B. Kokate
- , Katarzyna Ciuba
- & Pekka Lappalainen
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Article
| Open AccessTwo Rac1 pools integrate the direction and coordination of collective cell migration
Previous studies suggested a chemokine receptor governed gradient of Rac1 activity is essential for collective guidance of Drosophila border cells. Here, Zhou et al. report that two distinct Rac1 pools at protrusions and cables, not Rac1 activity gradient, integrate the direction and coordination for collective guidance.
- Sijia Zhou
- , Peng Li
- & Xiaobo Wang