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| Open AccessHistone functions as a cell-surface receptor for AGEs
Advanced glycation end products (AGEs) are believed to be pathogenic molecules that mediate pro-inflammatory responses. Here the authors identify histone as a cell-surface receptor for AGEs and show that AGEs may also be involved in the homeostatic response via binding to histone.
- Masanori Itakura
- , Kosuke Yamaguchi
- & Koji Uchida
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Article
| Open AccessTransgenic Anopheles mosquitoes expressing human PAI-1 impair malaria transmission
Plasmodium gametes and sporozoites activate surface-bound plasminogen to plasmin that degrades extracellular matrix barriers, therewith facilitating parasite motility in mosquitoes and mammalian hosts. To control malaria transmission, Pascini et al. generate Anopheles stephensi transgenic mosquitoes constitutively secreting human plasminogen activator inhibitor 1 in midgut and/or saliva which leads to inhibition of plasminogen activation and a reduction in oocyst intensity, infection prevalence, and transmission.
- Tales V. Pascini
- , Yeong Je Jeong
- & Joel Vega-Rodríguez
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Article
| Open AccessMetabolic control of progenitor cell propagation during Drosophila tracheal remodeling
Tracheal remodeling is a key step during Drosophila metamorphosis. Here they report that tracheal progenitor cells are activated through Yorkie-dependent proliferation and migration, which is induced by metabolic deficit and insulin signaling.
- Yue Li
- , Pengzhen Dong
- & Hai Huang
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Article
| Open AccessTopography-induced large-scale antiparallel collective migration in vascular endothelium
The physical environment dictates the emergence of specific patterns of collective cell migration. Here, authors show that unconfined endothelial monolayers on microgroove substrates exhibit an original pattern of antiparallel cell streams.
- Claire Leclech
- , David Gonzalez-Rodriguez
- & Abdul I. Barakat
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Article
| Open AccessShielding of actin by the endoplasmic reticulum impacts nuclear positioning
The nucleus connects to the actin cytoskeleton for nuclear movement in migrating cells. Here, the authors show that the endoplasmic reticulum shields actin cables to generate asymmetric nucleo-cytoskeleton connections for nuclear positioning.
- Cátia Silva Janota
- , Andreia Pinto
- & Edgar R. Gomes
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Article
| Open AccessPurine nucleotide depletion prompts cell migration by stimulating the serine synthesis pathway
Nucleotides are essential for different biological processes and have been also associated to cancer development. Depleting cellular nucleotides is a strategy commonly employed to target cancers. Here, the authors show that purine depletion induces serine synthesis to promote cancer cell migration and metastasis.
- Mona Hoseini Soflaee
- , Rushendhiran Kesavan
- & Gerta Hoxhaj
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Article
| Open AccessMechanical loading of intraluminal pressure mediates wound angiogenesis by regulating the TOCA family of F-BAR proteins
Chemical and mechanical cues coordinately regulate angiogenesis. Here, the authors show that blood flow-driven intraluminal pressure regulates wound angiogenesis. Findings indicate that TOCA family of F-BAR proteins act as actin regulators required for endothelial cell migration and sense mechanical cell stretching to regulate wound angiogenesis.
- Shinya Yuge
- , Koichi Nishiyama
- & Shigetomo Fukuhara
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Article
| Open AccessCalcium bursts allow rapid reorganization of EFhD2/Swip-1 cross-linked actin networks in epithelial wound closure
Calcium serves as an important second messenger in signal transduction to the actin cytoskeleton. Here, we identify EFhD2/Swip-1 as a calcium-dependent actin cross-linker promoting rapid reorganization of actin networks in epithelial wound closure.
- Franziska Lehne
- , Thomas Pokrant
- & Sven Bogdan
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Article
| Open AccessMechanism of integrin activation by talin and its cooperation with kindlin
The authors report here that talin and kindlin, the two key integrin binders and activators, are bridged by paxillin to induce microclustering of integrins to potently bind to multivalent extracellular ligand and trigger rapid cell attachment.
- Fan Lu
- , Liang Zhu
- & Jun Qin
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Article
| Open AccessPD-L1 signaling selectively regulates T cell lymphatic transendothelial migration
The Programmed death-1 (PD-1) and its ligand PD-L1 are critical checkpoints in the regulation of immune responses. Here the authors implicate PD-L1 signalling at lymphatic endothelium in the regulation of transendothelial migration of T cells.
- Wenji Piao
- , Lushen Li
- & Jonathan S. Bromberg
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Article
| Open AccessMolecular mechanism of Arp2/3 complex inhibition by Arpin
The Arp2/3 complex inhibitor Arpin controls cell migration by interrupting a feedback loop involving Rac-WAVE-Arp2/3 complex Here, the authors use structural, biochemical, and cellular studies to reveal Arpin’s mechanism of inhibition.
- Fred E. Fregoso
- , Trevor van Eeuwen
- & Roberto Dominguez
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Article
| Open AccessCyclic AMP signalling and glucose metabolism mediate pH taxis by African trypanosomes
African trypanosomes collectively move in a process called social motility. Here, the authors show that procyclic forms acidify their environment as a consequence of glucose metabolism, generating pH gradients by diffusion that are sensed via cyclic AMP signalling. Parasite mutants defective in cAMP signaling are inhibited in fly infection.
- Sebastian Shaw
- , Sebastian Knüsel
- & Isabel Roditi
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Article
| Open AccessKRas-transformed epithelia cells invade and partially dedifferentiate by basal cell extrusion
The ability to visualise stochastic invasion events is limited in murine models of metastatic cancers. Here the authors use a transparent zebrafish epidermis model to follow the invasion events of K-Ras transformed epithelial cells and show that these cells invade through basal cell extrusion.
- John Fadul
- , Teresa Zulueta-Coarasa
- & Jody Rosenblatt
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Article
| Open AccessNon-canonical Wnt signaling promotes directed migration of intestinal stem cells to sites of injury
Stem cell migration is critical during adult tissue regeneration. Here, the authors demonstrate that enteroendocrine cells coordinate stem cell migration towards sites of injury in the Drosophila intestine by activating non-canonical Wnt signaling.
- Daniel Jun-Kit Hu
- , Jina Yun
- & Heinrich Jasper
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Article
| Open AccessNuclear-capture of endosomes depletes nuclear G-actin to promote SRF/MRTF activation and cancer cell invasion
Effective delivery of signals from the cell surface to the nucleus is a key to activate gene transcription. Here, the authors show how endosomes containing EphA2 are transported and captured at the nuclear surface, triggering depletion of G-actin from the nucleus and activating MRTF signalling.
- Sergi Marco
- , Matthew Neilson
- & Jim C. Norman
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Article
| Open AccessG-protein-coupled receptor P2Y10 facilitates chemokine-induced CD4 T cell migration through autocrine/paracrine mediators
P2Y10 is a G-protein-coupled receptor that is expressed in CD4 T cells. Here authors show that its ligands, lysophosphatidylserine and ATP, are induced in T cells upon chemokine stimulation and regulate RhoA activation and migration through an autocrine/paracrine loop.
- Malarvizhi Gurusamy
- , Denise Tischner
- & Nina Wettschureck
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Article
| Open AccessOptogenetic control of receptors reveals distinct roles for actin- and Cdc42-dependent negative signals in chemotactic signal processing
Here the authors use optogenetic tools to directly measure spatial signal processing in leukocyte chemotaxis. Their results reveal the importance of multiple negative feedback loops for maintaining spatial information in chemotaxis.
- George R. R. Bell
- , Esther Rincón
- & Sean R. Collins
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Article
| Open AccessDirectional reorientation of migrating neutrophils is limited by suppression of receptor input signaling at the cell rear through myosin II activity
Neutrophils migrate with remarkably stable front-rear polarization. Using optogenetic receptor control to induce reversal of polarization in restrictive microfluidic channels, the authors find that myosin II promotes this stability by suppressing transmission of receptor inputs at the cell rear.
- Amalia Hadjitheodorou
- , George R. R. Bell
- & Julie A. Theriot
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Article
| Open AccessThe EMT activator ZEB1 accelerates endosomal trafficking to establish a polarity axis in lung adenocarcinoma cells
The way in which metastatic tumour cells control endocytic vesicular trafficking networks to establish a front-rear polarity axis that facilitates motility remains unclear. Here, the authors show that the EMT activator ZEB1 influences vesicular trafficking dynamics to execute cell polarity change.
- Priyam Banerjee
- , Guan-Yu Xiao
- & Jonathan M. Kurie
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Article
| Open AccessHomeostatic membrane tension constrains cancer cell dissemination by counteracting BAR protein assembly
Changes in cell mechanics contribute to cancer cell dissemination. Here the authors show that high plasma membrane (PM) tension inhibits cancer dissemination by counteracting mechanosensitive BAR family protein assembly, while restoration of PM tension phenotypically convert malignant cells into a non-motile epithelial cell state.
- Kazuya Tsujita
- , Reiko Satow
- & Toshiki Itoh
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Article
| Open AccessNance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration
Cell migration is essential for many physiological processes. Its deregulation causes cancer metastasis and it is not well understood how it is tightly controlled. We identify NHSL1 as a negative regulator of actin nucleating Scar/WAVE-Arp2/3 complexes, cell protrusion stability, and cell migration.
- Ah-Lai Law
- , Shamsinar Jalal
- & Matthias Krause
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Article
| Open AccessMechanosensitive recruitment of stator units promotes binding of the response regulator CheY-P to the flagellar motor
It is unclear how bacterial cells adapt the reversible switching of flagellar motor rotation to environments of different viscosities. Here, Antani et al. show that flagellar mechanosensors allosterically control the motor’s binding affinity for the chemotaxis response regulator, CheY-P, to adapt flagellar switching over varying viscous loads.
- Jyot D. Antani
- , Rachit Gupta
- & Pushkar P. Lele
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Article
| Open AccessA barbed end interference mechanism reveals how capping protein promotes nucleation in branched actin networks
The assembly of branched actin networks depends on the heterodimeric capping protein CP/CapZ. Combining cryoEM, in vitro reconstitution and cell biological assays, the authors show that CP not only prevents actin filament elongation but also selectively masks actin filament ends to promote nucleation.
- Johanna Funk
- , Felipe Merino
- & Peter Bieling
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Article
| Open AccessTMEM16F and dynamins control expansive plasma membrane reservoirs
Cells locally expand and retract their surface in response to environmental factors such as changes in membrane tension. Here the authors show the membrane adapter, dynamin2, locally constricts surface membrane to form an isolated but contiguous membrane reservoir that can open upon phospholipid scrambling via TMEM16F.
- Christine Deisl
- , Donald W. Hilgemann
- & Michael Fine
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Article
| Open AccessPulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional
Environmental and genetic risk factors affect the distal airway epithelium in idiopatic pulmonary fibrosis (IPF) but the role of the epithelium in IPF remains unclear. Here the authors show that pathologic activation of the ERBB-YAP axis induces dynamic and structural dysfunction in the distal airway epithelium eliciting a pro-fibrotic phenotype in mesenchymal cells.
- Ian T. Stancil
- , Jacob E. Michalski
- & David A. Schwartz
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Article
| Open AccessCell migration guided by long-lived spatial memory
Cells can modify their environment by depositing biochemical signals or mechanically remodelling the extracellular matrix; the impact of such self-induced environmental perturbations on cell trajectories at various scales remains unexplored. Here authors show that motile cells leave long-lived physicochemical footprints along their way, which determine their future path.
- Joseph d’Alessandro
- , Alex Barbier--Chebbah
- & Benoît Ladoux
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Article
| Open AccessLasp1 regulates adherens junction dynamics and fibroblast transformation in destructive arthritis
Fibroblast-like synoviocytes are important mediators of joint pathology in rheumatoid arthritis (RA). Here the authors show that Lasp1 is epigenetically regulated and highly expressed by these cells in RA and its deletion can limit joint pathology in a mouse model of inflammatory arthritis.
- Denise Beckmann
- , Anja Römer-Hillmann
- & Adelheid Korb-Pap
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Article
| Open AccessThe lysosomal Ragulator complex plays an essential role in leukocyte trafficking by activating myosin II
Myosin II–mediated contractility is required for leukocyte migration. Here, authors show that lysosomes are involved in leukocyte migration by providing the platform where Ragulator complex interacts with the myosin phosphatase Rho-interacting protein (MPRIP) independently of mTORC1 and interferes with the interaction between MPRIP and a subunit of myosin light chain phosphatase (MLCP).
- Takeshi Nakatani
- , Kohei Tsujimoto
- & Atsushi Kumanogoh
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Article
| Open AccessBAD regulates mammary gland morphogenesis by 4E-BP1-mediated control of localized translation in mouse and human models
Preventing phosphorylation of BAD (3SA) in mouse models and human cells inhibits mammary gland development, acting by disrupting 4E-BP1- mediated translation and affecting focal adhesion/protrusion stability, cell migration and ductal tubulogenesis.
- John Maringa Githaka
- , Namita Tripathi
- & Ing Swie Goping
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Article
| Open AccessA junctional PACSIN2/EHD4/MICAL-L1 complex coordinates VE-cadherin trafficking for endothelial migration and angiogenesis
Communication between endothelial leader and follower cells during collective cell migration is crucial for vascular development. Here, the authors show that PACSIN2 guides collective cell migration and angiogenesis by recruiting a protein trafficking complex to asymmetric cell-cell junctions, controlling local junction plasticity.
- Tsveta S. Malinova
- , Ana Angulo-Urarte
- & Stephan Huveneers
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Article
| Open AccessLoss of Ambra1 promotes melanoma growth and invasion
The absence of scaffold protein Ambra1 leads to hyperproliferation and growth in mouse models. Here the authors show that Ambra1 deficiency accelerates melanoma growth and increases metastasis in mouse models of melanoma through FAK1 hyperactivation.
- Luca Di Leo
- , Valérie Bodemeyer
- & Francesco Cecconi
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Article
| Open AccessAn ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism
The signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive responses occur is unclear. Here, the authors show that alternate isoforms of the ARF GTPase exchange factor IQSEC1 direct phosphoinositide metabolism to control this switch.
- Marisa Nacke
- , Emma Sandilands
- & David M. Bryant
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Article
| Open AccessFilopodia-based contact stimulation of cell migration drives tissue morphogenesis
Contact stimulation of migration drives tissue morphogenesis. Here the authors report that filopodia-based contact-dependent asymmetry of cell–matrix adhesion drives directional movement, whereas contractile actin cables contribute to the integrity of the migrating cell cluster in the myotubes of Drosophila developing testes.
- Maik C. Bischoff
- , Sebastian Lieb
- & Sven Bogdan
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Article
| Open AccessSTIM-Orai1 signaling regulates fluidity of cytoplasm during membrane blebbing
The cytoplasm in mammalian cells is considered homogeneous. Here authors report that the cytoplasmic fluidity is regulated in the blebbing cells, which is regulated by calcium concentration in the expanding blebs and involves the STIM-Orai1 pathway.
- Kana Aoki
- , Shota Harada
- & Junichi Ikenouchi
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Article
| Open Accessβ-Pix-dependent cellular protrusions propel collective mesoderm migration in the mouse embryo
Mesodermal directional cell migration is needed to establish body plan but how this is regulated is unclear. Here, the authors show that loss of the guanine nucleotide exchange factor for Rac1 and Cdc42, β-Pix, at mouse gastrulation disrupts the orderly, collective anterior migration of mesoderm cells due to defective cell protrusions.
- Tatiana Omelchenko
- , Alan Hall
- & Kathryn V. Anderson
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Article
| Open AccessBiased localization of actin binding proteins by actin filament conformation
The assembly of actin filaments into distinct cytoskeletal structures plays a critical role in cell physiology. Here, the authors use a combination of live cell imaging and in vitro single molecule binding measurements to show that tandem calponin homology domains (CH1–CH2) are sensitive to actin filament conformation, biasing their subcellular localization.
- Andrew R. Harris
- , Pamela Jreij
- & Daniel A. Fletcher
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Article
| Open AccessVascular surveillance by haptotactic blood platelets in inflammation and infection
Breakdown of vascular barriers is a major complication of inflammatory diseases. However, the mechanisms underlying platelet recruitment to inflammatory micro-environments remains unclear. Here, the authors identify haptotaxis as a key effector function of immune-responsive platelets
- Leo Nicolai
- , Karin Schiefelbein
- & Florian Gaertner
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Article
| Open AccessE-cadherin focuses protrusion formation at the front of migrating cells by impeding actin flow
The arrival of migratory cells at their targets relies on following precise routes within tissues. Here the authors demonstrate that the cell adhesion molecule E-cadherin can control the path of cell migration by confining the site where bleb-type protrusions form within the cell front.
- Cecilia Grimaldi
- , Isabel Schumacher
- & Erez Raz
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Article
| Open AccessSiah2 integrates mitogenic and extracellular matrix signals linking neuronal progenitor ciliogenesis with germinal zone occupancy
In neural development, progenitors transition from a proliferative to a differentiated state. Here, the authors show that cerebellar granule neurons retract primary cilia as they exit their proliferative niche upon decreased ECM engagement, enabling radial migration due to loss of Shh sensitivity.
- Taren Ong
- , Niraj Trivedi
- & David J. Solecki
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Article
| Open AccessIn primary airway epithelial cells, the unjamming transition is distinct from the epithelial-to-mesenchymal transition
During repair, development, or cancer metastasis, epithelial cells can become migratory through partial or full epithelial to mesenchymal transition (EMT). Here, the authors report that differentiated epithelial collectives may undergo cooperative and collective migration without evidence of partial EMT through an unjamming transition (UJT).
- Jennifer A. Mitchel
- , Amit Das
- & Jin-Ah Park
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Article
| Open AccessATR is essential for preservation of cell mechanics and nuclear integrity during interstitial migration
The nucleus is a mechanically stiff organelle of the cell and the DNA damage response protein ATR can localize to the nuclear envelope upon mechanical stress. Here, the authors show that ATR may contribute to the integrity of the nuclear envelope and may play a role in cell migration.
- Gururaj Rao Kidiyoor
- , Qingsen Li
- & Marco Foiani
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Article
| Open AccessT-Plastin reinforces membrane protrusions to bridge matrix gaps during cell migration
In vivo, cells migrate across a diverse landscape of extracellular matrix containing gaps which present a challenge for cells to protrude across. Here, the authors show that T-Plastin strengthens protrusive actin networks to promote protrusion, extracellular matrix gap-bridging, and cell migration.
- Damien Garbett
- , Anjali Bisaria
- & Tobias Meyer
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Article
| Open AccessCollectively stabilizing and orienting posterior migratory forces disperses cell clusters in vivo
During development, primordial germ cell clusters undergo dispersal but how cell–cell adhesion and contractility are coordinated during this process in vivo is unclear. Here, the authors show that Drosophila primordial germ cells utilize migratory forces to disperse through G-protein coupled receptor mediated collective guidance of front-back polarity outwards from the cluster.
- B. Lin
- , J. Luo
- & R. Lehmann
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Article
| Open AccessCosmc controls B cell homing
Migration and homing of B cells to lymph nodes are important for B cell functions, but their regulation is poorly understood. Here, the authors show that B cell-specific deletion of Cosmc results in decreased protein O-glycosylation, loss of B cell homing to both lymphoid and nonlymphoid organs, and altered transendothelial migration implicated in this loss.
- Junwei Zeng
- , Mahmoud Eljalby
- & Richard D. Cummings
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Article
| Open AccessPreservation of microvascular barrier function requires CD31 receptor-induced metabolic reprogramming
The mechanisms that restore endothelial barrier integrity following inflammation-induced breaching are incompletely understood. Here the authors show that the CD31 immune receptor contributes to reestablishing vascular integrity via its effects on endothelial cell metabolism.
- Kenneth C. P. Cheung
- , Silvia Fanti
- & Federica M. Marelli-Berg
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Article
| Open AccessDissemination of RasV12-transformed cells requires the mechanosensitive channel Piezo
Drosophila tumours can be utilised to study the mechanisms of cell dissemination. Here, the authors use Drosophila midgut to examine the course of RasV12-transformed cell dissemination from midgut into circulation, which requires the actions of invasive protrusions and the mechanosensitive channel Piezo.
- Jiae Lee
- , Alejandra J. H. Cabrera
- & Young V. Kwon
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Article
| Open AccessDiaphanous-related formin mDia2 regulates beta2 integrins to control hematopoietic stem and progenitor cell engraftment
Bone marrow engraftment of haematopoietic stem and progenitor cells (HSPCs) requires homing and lodgement to the niche. Here, the authors show that mDia2 is required for HSPC polarization, nuclear MAL, and SRF-induced beta2 integrin expression during transendothelial migration of HSPCs required for engraftment.
- Yang Mei
- , Xu Han
- & Peng Ji
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Article
| Open AccessA self-sustaining endocytic-based loop promotes breast cancer plasticity leading to aggressiveness and pro-metastatic behavior
It is unclear if genetic alterations in endocytic proteins play a causal role in high incidence human cancers. Here, the authors report the oncogenic role of Epsin3 (EPN3) in breast cancer, and show EPN3 to drive tumorigenesis through induction of a partial epithelial mesenchymal transition state and a TGFβ-dependent regulatory loop that promotes cellular plasticity and invasive behaviour.
- Irene Schiano Lomoriello
- , Giovanni Giangreco
- & Pier Paolo Di Fiore
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Article
| Open AccessEpithelial invagination by a vertical telescoping cell movement in mammalian salivary glands and teeth
Mechanisms that regulate epithelial bending mainly link to cell shape changes, for example, the formation of wedge shaped cells. Here, the authors identify a different cell behaviour in the salivary glands and teeth where initial invagination arises by a coordinated vertical cell movement.
- Jingjing Li
- , Andrew D. Economou
- & Jeremy B. A. Green