Abstract:
:Up-regulation of the cytoskeleton linker protein ezrin frequently occurs in aggressive cancer types and is closely linked with metastatic progression. However, the underlying molecular mechanisms detailing how ezrin is involved in the invasive and metastatic phenotype remain unclear. Here we report a novel function of ezrin in regulating focal adhesion (FA) and invadopodia dynamics, two key processes required for efficient invasion to occur. We show that depletion of ezrin expression in invasive breast cancer cells impairs both FA and invadopodia turnover. We also demonstrate that ezrin-depleted cells display reduced calpain-mediated cleavage of the FA and invadopodia-associated proteins talin, focal adhesion kinase (FAK), and cortactin and reduced calpain-1-specific membrane localization, suggesting a requirement for ezrin in maintaining proper localization and activity of calpain-1. Furthermore, we show that ezrin is required for cell directionality, early lung seeding, and distant organ colonization but not primary tumor growth. Collectively our results unveil a novel mechanism by which ezrin regulates breast cancer cell invasion and metastasis.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Hoskin V,Szeto A,Ghaffari A,Greer PA,Côté GP,Elliott BEdoi
10.1091/mbc.E14-12-1584subject
Has Abstractpub_date
2015-10-01 00:00:00pages
3464-79issue
19eissn
1059-1524issn
1939-4586pii
mbc.E14-12-1584journal_volume
26pub_type
杂志文章abstract::XMAP215/Dis1 proteins are conserved tubulin-binding TOG-domain proteins that regulate microtubule (MT) plus-end dynamics. Here we show that Alp14, a XMAP215 orthologue in fission yeast, Schizosaccharomyces pombe, has properties of a MT polymerase. In vivo, Alp14 localizes to growing MT plus ends in a manner independen...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E12-03-0205
更新日期:2012-08-01 00:00:00
abstract::Although the distribution of the cation-independent mannose 6-phosphate receptor (CI-MPR) has been well studied, its intracellular itinerary and trafficking kinetics remain uncertain. In this report, we describe the endocytic trafficking and steady-state localization of a chimeric form of the CI-MPR containing the ect...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e03-07-0497
更新日期:2004-02-01 00:00:00
abstract::Cytokinesis in metazoan cells requires a set of antiparallel microtubules that become bundled upon anaphase onset to form a structure known as the central spindle. Bundling of these microtubules requires a protein complex, centralspindlin, that consists of the CYK-4/MgcRacGAP Rho-family GTPase-activating protein and t...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e07-05-0468
更新日期:2007-12-01 00:00:00
abstract::A novel selection scheme has been developed to isolate bloodstream forms of Trypanosoma brucei, which are defective in their ability to differentiate to the procyclic stage. Detailed characterization of one selected cell line (defective in differentiation clone 1 [DiD-1]) has demonstrated that these cells are indistin...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.11.5.1905
更新日期:2000-05-01 00:00:00
abstract::SPOP, speckle-type POZ protein is a substrate adaptor protein of the Cullin-3/RING ubiquitin E3 complex. The spop gene is the most commonly point mutated in human primary prostate cancers, but the pathological contribution of the SPOP mutations remains unclear. In this study, we investigated several known factors that...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E19-08-0456
更新日期:2020-03-15 00:00:00
abstract::Despite the importance of epithelial cell contacts in determining cell behavior, we still lack a detailed understanding of the assembly and disassembly of intercellular contacts. Here we examined the role of the catalytic activity of the Src family kinases at epithelial cell contacts in vitro. Like E- and P-cadherin, ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.11.1.51
更新日期:2000-01-01 00:00:00
abstract::The tail of the yeast myosin V encoded by Myo2p is known to bind several receptors for cargo delivery along polarized actin cables. However, it is not known how Myo2p activity is regulated or how it selects between cargoes. Here we show that Myo2p is reversibly phosphorylated in vivo. A short peptide at the N-terminal...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e05-09-0872
更新日期:2006-04-01 00:00:00
abstract::The location of the phospholipase C beta 1-isoform (PLC-beta 1) in the mouse oocyte and its role in the resumption of meiosis were examined. We used specific monoclonal antibodies to monitor the in vitro dynamics of the subcellular distribution of the enzyme from the release of the oocyte from the follicle until break...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.11.12.4369
更新日期:2000-12-01 00:00:00
abstract::Elicitins secreted by phytopathogenic Phytophthora spp. are proteinaceous elicitors of plant defense mechanisms and were demonstrated to load, carry, and transfer sterols between membranes. The link between elicitor and sterol-loading properties was assessed with the use of site-directed mutagenesis of the 47 and 87 c...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.12.9.2825
更新日期:2001-09-01 00:00:00
abstract::Matrix metalloproteinases (MMPs) are extracellular proteases highly expressed at wound sites. However, the precise function of MMPs during reepithelialization in vivo has been elusive in mammalian models because of the high level of redundancy among the 24 mammalian MMPs. For this reason we used Drosophila melanogaste...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E11-09-0745
更新日期:2012-03-01 00:00:00
abstract::The orderly progression through the cell division cycle is of paramount importance to all organisms, as improper progression through the cycle could result in defects with grave consequences. Previously, our lab has shown that model eukaryotes such as Saccharomyces cerevisiae, Caenorhabditis elegans, and Danio rerio a...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e09-07-0614
更新日期:2010-07-01 00:00:00
abstract::In vitro studies suggest that the Barren protein may function as an activator of DNA topoisomerase II and/or as a component of the Xenopus condensin complex. To better understand the role of Barren in vivo, we generated conditional alleles of the structural gene for Barren (BRN1) in Saccharomyces cerevisiae. We show t...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.11.4.1293
更新日期:2000-04-01 00:00:00
abstract::RhoA is a small guanosine-5'-triphosphatase (GTPase) suggested to be essential for cytokinesis, stress fiber formation, and epithelial cell-cell contacts. In skin, loss of RhoA was suggested to underlie pemphigus skin blistering. To analyze RhoA function in vivo, we generated mice with a keratinocyte-restricted deleti...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E09-10-0859
更新日期:2011-03-01 00:00:00
abstract::Cellular responses to environmental changes occur on different levels. We investigated the translational response of yeast cells after mild hyperosmotic shock by isolating mRNA associated with multiple ribosomes (polysomes) followed by array analysis. Globally, recruitment of preexisting mRNAs to ribosomes (translatio...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E10-01-0006
更新日期:2010-09-01 00:00:00
abstract::Early endosomes in PC12 cells are an important site for the formation of synaptic-like microvesicles and constitutive recycling vesicles. By immunogold electron microscopy, the small GTPase rab4 was localized to early endosomes and numerous small vesicles in the cell periphery and Golgi area of PC12 cells. Overexpress...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.12.11.3703
更新日期:2001-11-01 00:00:00
abstract::Melanosomes are tissue-specific organelles within which melanin is synthesized and stored. The melanocyte-specific glycoprotein Pmel17 is enriched in the lumen of premelanosomes, where it associates with characteristic striations of unknown composition upon which melanin is deposited. However, Pmel17 is synthesized as...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.12.11.3451
更新日期:2001-11-01 00:00:00
abstract::The ubiquitin-like hPLIC proteins can associate with proteasomes, and hPLIC overexpression can specifically interfere with ubiquitin-mediated proteolysis (Kleijnen et al., 2000). Because the hPLIC proteins can also interact with certain E3 ubiquitin protein ligases, they may provide a link between the ubiquitination a...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e02-11-0766
更新日期:2003-09-01 00:00:00
abstract::The skin's epidermis is a multilayered epithelial tissue and the first line of defense against mechanical stress. Its barrier function depends on an integrated assembly and reorganization of cell-matrix and cell-cell junctions in the basal layer and on different intercellular junctions in suprabasal layers. However, h...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E17-06-0387
更新日期:2018-09-15 00:00:00
abstract::In many insects, development of the oocyte arrests temporarily just before vitellogenesis, the period when vitellogenins (yolk proteins) accumulate in the oocyte. Following hormonal and environmental cues, development of the oocyte resumes, and endocytosis of vitellogenins begins. An essential component of yolk uptake...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.11.2.511
更新日期:2000-02-01 00:00:00
abstract::Macrophage fusion resulting in the formation of multinucleated giant cells occurs in a variety of chronic inflammatory diseases, yet the mechanism responsible for initiating this process is unknown. Here, we used live cell imaging to show that actin-based protrusions at the leading edge initiate macrophage fusion. Pha...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E19-01-0009
更新日期:2019-08-01 00:00:00
abstract::Functionally different subsets of actin filament arrays contribute to cellular organization and motility. We report the identification of a novel subset of loose actin filament arrays through regulated association with the widely expressed protein SWAP-70. These loose actin filament arrays were commonly located behind...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e03-01-0043
更新日期:2003-08-01 00:00:00
abstract::Rho GTPases share a common inhibitor, Rho guanine nucleotide dissociation inhibitor (RhoGDI), which regulates their expression levels, membrane localization, and activation state. The selective dissociation of individual Rho GTPases from RhoGDI ensures appropriate responses to cellular signals, but the underlying mech...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E12-01-0026
更新日期:2012-10-01 00:00:00
abstract::Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase protein localized to regions called focal adhesions, which are contact points between cells and the extracellular matrix. FAK protein acts as a scaffold to transfer adhesion-dependent and growth factor signals into the cell. Increased FAK expression is linke...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E10-12-0932
更新日期:2011-07-01 00:00:00
abstract::Mitochondrial decline is a hallmark of aging, and cells are equipped with many systems to regulate mitochondrial structure and function in response to stress and metabolic alterations. Here, using budding yeast, we identify a proteolytic pathway that contributes to alterations in mitochondrial structure in aged cells ...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.E19-02-0094
更新日期:2019-08-01 00:00:00
abstract::Chemoattractants induce neutrophil polarization through localized polymerization of F-actin at the leading edge. The suppression of rear and lateral protrusions is required for efficient chemotaxis and involves the temporal and spatial segregation of signaling molecules. We have previously shown that the intracellular...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e06-09-0876
更新日期:2007-03-01 00:00:00
abstract::The sorting of most integral membrane proteins into the lumenal vesicles of multivesicular bodies (MVBs) is dependent on the attachment of ubiquitin (Ub) to their cytosolic domains. However, Ub is not required for sorting of Sna3, an MVB vesicle cargo protein in yeast. We show that Sna3 circumvents Ub-mediated recogni...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e06-08-0663
更新日期:2007-02-01 00:00:00
abstract::The tumor suppressor protein p53 mediates stress-induced growth arrest or apoptosis and plays a major role in safeguarding genome integrity. In response to DNA damage, p53 can be modified at multiple sites by phosphorylation and acetylation. We report on the characterization of p53 C-terminal phosphorylation by CHK1 a...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e04-08-0689
更新日期:2005-04-01 00:00:00
abstract::Timely degradation of regulatory proteins by the ubiquitin proteolytic pathway (UPP) is an established paradigm of cell cycle regulation during the G2/M and G1/S transitions. Less is known about roles for the UPP during S phase. Here we present evidence that dynamic cell cycle-dependent changes in levels of UbcH7 regu...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e08-01-0036
更新日期:2009-01-01 00:00:00
abstract::The NUDF protein of the filamentous fungus Aspergillus nidulans functions in the cytoplasmic dynein pathway. It binds several proteins, including the NUDE protein. Green fluorescent protein-tagged NUDF and NUDA (dynein heavy chain) localize to linearly moving dashes ("comets") that coincide with microtubule ends. Here...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.e02-06-0359
更新日期:2003-03-01 00:00:00
abstract::We recently established an in vitro assay that monitors the fusion between latex-bead phagosomes and endocytic organelles in the presence of J774 macrophage cytosol (). Here, we show that different reagents affecting the actin cytoskeleton can either inhibit or stimulate this fusion process. Because the membranes of p...
journal_title:Molecular biology of the cell
pub_type: 杂志文章
doi:10.1091/mbc.12.1.155
更新日期:2001-01-01 00:00:00