Abstract:
:Chloride intracellular channel 3 (CLIC3) drives invasiveness of pancreatic and ovarian cancer by acting in concert with Rab25 to regulate the recycling of α5β1 integrin from late endosomes to the plasma membrane. Here, we show that in two estrogen receptor (ER)-negative breast cancer cell lines, CLIC3 has little influence on integrin recycling, but controls trafficking of the pro-invasive matrix metalloproteinase MT1-MMP (also known as MMP14). In MDA-MB-231 cells, MT1-MMP and CLIC3 are localized primarily to late endosomal/lysosomal compartments located above the plane of adhesion and near the nucleus. MT1-MMP is transferred from these late endosomes to sites of cell-matrix adhesion in a CLIC3-dependent fashion. Correspondingly, CLIC3-knockdown opposes MT1-MMP-dependent invasive processes. These include the disruption of the basement membrane as acini formed from MCF10DCIS.com cells acquire invasive characteristics in 3D culture, and the invasion of MDA-MB-231 cells into Matrigel or organotypic plugs of type I collagen. Consistent with this, expression of CLIC3 predicts poor prognosis in ER-negative breast cancer. The identification of MT1-MMP as a cargo of a CLIC3-regulated pathway that drives invasion highlights the importance of late endosomal sorting and trafficking in breast cancer.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Macpherson IR,Rainero E,Mitchell LE,van den Berghe PV,Speirs C,Dozynkiewicz MA,Chaudhary S,Kalna G,Edwards J,Timpson P,Norman JCdoi
10.1242/jcs.135947subject
Has Abstractpub_date
2014-09-15 00:00:00pages
3893-901issue
Pt 18eissn
0021-9533issn
1477-9137pii
jcs.135947journal_volume
127pub_type
杂志文章abstract::NF-kappaB plays a central role in mediating pathogen and cytokine-stimulated gene transcription. NF-kappaB repressing factor (NRF) has been shown to interact with specific negative regulatory DNA elements (NRE) to mediate transcriptional repression by inhibition of the NF-kappaB activity at certain promoters. mRNA abl...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.01129
更新日期:2004-07-15 00:00:00
abstract::Although loss of cell-cell adhesion and gain of invasive properties play a crucial role in the malignant progression of epithelial tumours, the molecular signals that trigger these processes have not been fully elucidated. In light of the well-established relationship between chronic inflammation and cancer, we hypoth...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.02467
更新日期:2005-08-01 00:00:00
abstract::Distribution of mitochondria as well as other intracellular organelles in mammalian cells is regulated by interphase microtubules. Here, we demonstrate a role of microtubules in the mitochondrial biogenesis using various microtubule-active drugs and human osteosarcoma cell line 143B cells and rat liver-derived RL-34 c...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2001-01-01 00:00:00
abstract::BMP2 stimulates bone formation and signals preferably through BMP receptor (BMPR) 1A, whereas GDF5 is a cartilage inducer and signals preferably through BMPR1B. Consequently, BMPR1A and BMPR1B are believed to be involved in bone and cartilage formation, respectively. However, their function is not yet fully clarified....
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.246934
更新日期:2020-08-21 00:00:00
abstract::Actin polymerization is a crucial process during sperm capacitation. We have recently described the participation of FAK during actin polymerization in guinea pig spermatozoa. However, the mechanism by which FAK mediates these processes is unknown. Our previous data have shown that MAPK1 (hereafter referred to as ERK2...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.239186
更新日期:2020-04-28 00:00:00
abstract::We have developed a procedure for sequential silver staining and in situ hybridization to analyze the relationship between the amount of rDNA present in nucleolar organizer regions, as estimated by in situ hybridization, and their level of expression, as estimated by the silver signal. For simplicity we used cells fro...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract::A number of structural and functional subnuclear compartments have been described, including regions exclusive of chromosomes previously hypothesized to form a reactive nuclear space. We have now explored this accessible nuclear space and interchromosomal nucleoplasmic domains experimentally using Xenopus vimentin eng...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract::In situ observations of the development of hippocampal and cortical neurons indicate that final axon-dendrite identity is defined at the time of generation of the first two, oppositely positioned, neurites. Quite differently, in vitro studies demonstrated that axonal fate is defined by the stochastic selection of one ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.023143
更新日期:2008-01-15 00:00:00
abstract::Rho GTPases and their downstream effectors regulate changes in the actin cytoskeleton that underlie cell motility and adhesion. They also participate, with RhoA, in the regulation of gene transcription by activating serum response factor (SRF)-mediated transcription from the serum response element (SRE). SRF-mediated ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.013557
更新日期:2008-02-15 00:00:00
abstract::Previously, we showed that an integral component of stored mRNP particles in Xenopus oocytes, Xp54, is a DEAD-box RNA helicase with ATP-dependent RNA-unwinding activity. Xp54 belongs to small family of helicases (DDX6) that associate with mRNA molecules encoding proteins required for progress through meiosis. Here we ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2002-01-15 00:00:00
abstract::The structure of a late endosomal compartment, which contains the bulk of the cation-independent mannose 6-phosphate receptor (MPR) in NRK cells, is documented using immunocytochemistry and cryo-sections, as well as conventional Epon sections. This compartment, which we refer to as the prelysosomal compartment (PLC), ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1990-03-01 00:00:00
abstract::Cell migration makes a fundamental contribution to both normal physiology and disease pathogenesis. Integrin engagement with extracellular ligands spatially controls, via the cyclical activation and deactivation of the small GTPase Rac1, the dynamic membrane protrusion and cytoskeletal reorganization events that are r...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.121988
更新日期:2013-09-15 00:00:00
abstract::RIF1 controls both DNA replication timing and the DNA double-strand break (DSB) repair pathway to maintain genome integrity. However, it remains unclear how RIF1 links these two processes following exposure to ionizing radiation (IR). Here, we show that inhibition of homologous recombination repair (HRR) by RIF1 occur...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.240036
更新日期:2020-06-22 00:00:00
abstract::Postsynaptic density protein 95 (PSD-95/SAP-90) is a palmitoylated membrane-associated guanylate kinase that oligomerizes and clusters ion channels and associated signaling machinery at excitatory synapses in brain. However, the mechanism for PSD-95 oligomerization and its relationship to ion channel clustering remain...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.00617
更新日期:2003-08-01 00:00:00
abstract::Eukaryotic flagella undertake different beat types as necessary for different functions; for example, the Leishmania parasite flagellum undergoes a symmetric tip-to-base beat for forward swimming and an asymmetric base-to-tip beat to rotate the cell. In multi-ciliated tissues or organisms, the asymmetric beats are coo...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.246637
更新日期:2020-10-22 00:00:00
abstract::Heparin-binding EGF-like growth factor (HB-EGF) is a ligand for EGF receptor (EGFR) and possesses the ability to signal in juxtacrine, autocrine and/or paracrine mode, with these alternatives being governed by the degree of proteolytic release of the ligand. Although the spatial range of diffusion of released HB-EGF i...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.058321
更新日期:2010-07-01 00:00:00
abstract::Regulated, programmed cell death is crucial for all multicellular organisms. Cell death is essential in many processes, including tissue sculpting during embryogenesis, development of the immune system and destruction of damaged cells. The best-studied form of programmed cell death is apoptosis, a process that require...
journal_title:Journal of cell science
pub_type: 杂志文章,评审
doi:10.1242/jcs.093575
更新日期:2014-05-15 00:00:00
abstract::The nonclaret disjunctional (ncd) protein is a kinesin-related microtubule motor protein that is encoded at the claret locus in Drosophila and is required for proper chromosome distribution in meiosis and early mitosis. The protein contains a region with 41% amino acid sequence identity to kinesin heavy chain, but tra...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1993-03-01 00:00:00
abstract::The large GTPase dynamin, long known for its role in endocytosis, has most recently been implicated as a facilitator of cell migration and invasion. Recent observations link dynamin to the cycle of membrane expansion and retraction essential for cell motility. Its role in actin polymerization, membrane deformation and...
journal_title:Journal of cell science
pub_type: 杂志文章,评审
doi:10.1242/jcs.02963
更新日期:2006-05-01 00:00:00
abstract::Nonsense-mediated mRNA decay (NMD) is an evolutionarily conserved mRNA surveillance system that degrades mRNA transcripts that harbour a premature translation-termination codon (PTC), thus reducing the synthesis of truncated proteins that would otherwise have deleterious effects. Although extensive research has identi...
journal_title:Journal of cell science
pub_type: 杂志文章,评审
doi:10.1242/jcs.120220
更新日期:2013-06-15 00:00:00
abstract::The protein kinase inhibitor H-7 prevents the assembly of tight junctions in cultured Madin Darby Canine Kidney (MDCK) epithelial cells (Balda et al. (1991) J. Membr. Biol. 122, 193-202; Nigam et al. (1991) Biochem. Biophys. Res. Commun. 181, 548-553); however, its mechanism of action is unknown. To understand the bas...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract::Integrins play a key role in regulating endothelial cell survival, migration and differentiated function during angiogenic blood-vessel remodeling. Integrin-linked kinase (ILK) is a multidomain protein that interacts with the cytoplasmic tail of integrin beta subunits and is thought to participate in integrin-mediated...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.01331
更新日期:2004-09-01 00:00:00
abstract::SNARE [soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptor] proteins control the membrane-fusion events of eukaryotic membrane-trafficking pathways. Specific vesicular and target SNAREs operate in specific trafficking routes, but the degree of specificity of SNARE functions is still elus...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.007948
更新日期:2007-09-15 00:00:00
abstract::Insect flight muscle has a large component (Tn-H) in the tropomyosin-troponin complex that is not present in vertebrate striated muscle thin filaments. Tn-H is shown by gold/Fab labelling to be present at regular intervals in insect flight muscle thin filaments. The Fab fragment of a monoclonal antibody to Tn-H was co...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
abstract::Previously, we have identified a class of retinal degeneration mutants in Drosophila in which the normally transient interaction between arrestin2 (Arr2) and rhodopsin is stabilized and the complexes are rapidly internalized into the cell body by receptor-mediated endocytosis. The accumulation of protein complexes in ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.03052
更新日期:2006-08-01 00:00:00
abstract::The cell nucleus is highly organized. Many nuclear functions are localized in discrete domains, suggesting that compartmentalization is an important aspect of the regulation and coordination of nuclear functions. We investigated the subnuclear distribution of the glucocorticoid receptor, a hormone-dependent transcript...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:1995-09-01 00:00:00
abstract::The model organism Neurospora crassa undergoes programmed cell death when exposed to staurosporine. Here, we show that staurosporine causes defined changes in cytosolic free Ca(2+) ([Ca(2+)]c) dynamics and a distinct Ca(2+) signature that involves Ca(2+) influx from the external medium and internal Ca(2+) stores. We i...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.152058
更新日期:2014-09-01 00:00:00
abstract::The path that RNA takes through nuclear pores was mapped using two high-resolution techniques. Unexpectedly, no RNA in HL60 cells was detected by immunogold labelling in the central axis of the pore complex on its way to the transporter at the nuclear membrane; instead, it was distributed around the sides, apparently ...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:
更新日期:2000-01-01 00:00:00
abstract::Coronins are conserved F-actin-binding proteins that are important for motility and actin dynamics. Unlike type I coronins, coronin 2A localizes to stress fibers and some focal adhesions, and is excluded from the leading edge. Depletion of coronin 2A in MTLn3 cells decreases cell motility and turnover of focal adhesio...
journal_title:Journal of cell science
pub_type: 杂志文章
doi:10.1242/jcs.051482
更新日期:2009-09-01 00:00:00
abstract::The development of DNA microarrays to study simultaneously the level of mRNA expressed from thousands of genes offers great promise to cell biologists. Microarrays can be used to gain detailed information about transcriptional changes involved in a specific pathway, potentially leading to the identification of novel c...
journal_title:Journal of cell science
pub_type: 杂志文章,评审
doi:
更新日期:2000-12-01 00:00:00