Abstract：
:Increased deposition of collagen in extracellular matrix (ECM) leads to increased tissue stiffness and occurs in breast tumors. When present, this increases tumor invasion and metastasis. Precisely how this deposition is regulated and maintained in tumors is unclear. Much has been learnt about mechanical signal transduction in cells, but transcriptional responses and the pathophysiological consequences are just becoming appreciated. Here, we show that the SNAIL1 (also known as SNAI1) protein level increases and accumulates in nuclei of breast tumor cells and cancer-associated fibroblasts (CAFs) following exposure to stiff ECM in culture and in vivo SNAIL1 is required for the fibrogenic response of CAFs when exposed to a stiff matrix. ECM stiffness induces ROCK activity, which stabilizes SNAIL1 protein indirectly by increasing intracellular tension, integrin clustering and integrin signaling to ERK2 (also known as MAPK1). Increased ERK2 activity leads to nuclear accumulation of SNAIL1, and, thus, avoidance of cytosolic proteasome degradation. SNAIL1 also influences the level and activity of YAP1 in CAFs exposed to a stiff matrix. This work describes a mechanism whereby increased tumor fibrosis can perpetuate activation of CAFs to sustain tumor fibrosis and promote tumor metastasis through regulation of SNAIL1 protein level and activity.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Zhang K,Grither WR,Van Hove S,Biswas H,Ponik SM,Eliceiri KW,Keely PJ,Longmore GDdoi
10.1242/jcs.180539subject
Has Abstractpub_date
2016-05-15 00:00:00pages
1989-2002issue
10eissn
0021-9533issn
1477-9137pii
jcs.180539journal_volume
129pub_type
杂志文章abstract：:A comparison of stained cytosolic proteins, in vivo 80 S ribosome translation products and in vitro translation products of poly(A)+ RNA from three species of Acetabularia was performed after characterization of their molecular weights and isoelectric points via two-dimensional electrophoresis. A total of 803 stained ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1983-03-01 00:00:00
abstract：:The extracellular matrix (ECM) regulates cell behavior by influencing cell proliferation, survival, shape, migration and differentiation. Far from being a static structure, the ECM is constantly undergoing remodeling--i.e. assembly and degradation--particularly during the normal processes of development, differentiati...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.006064
更新日期：2008-02-01 00:00:00
abstract：:A new mouse model has been developed to study the localisation and trafficking of the glucose transporter GLUT4 in muscle. The mouse line has specific expression of a GFP and HA-epitope-tagged version of GLUT4 under the control of a muscle-specific promoter. The exofacial HA-tag has enabled fluorescent labelling of on...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.041178
更新日期：2009-03-01 00:00:00
abstract：:Earlier reports have indicated that the pollen of Eucalyptus is mechanically robust and unusually resistant to the osmotic stress imposed by immersion in water. We have investigated some of the features of the germination mechanism in the pollen of E. rhodantha with a view to clarifying the role of pollen-wall special...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1985-02-01 00:00:00
abstract：:In the fission yeast Schizosaccharomyces pombe, a series of diploid mutants divides at smaller cell sizes than wild type. In these smaller strains, the mean gene concentration (defined by previous authors as the DNA to protein ratio) is higher than in wild type. Such an increase in gene concentration should also incre...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1979-02-01 00:00:00
abstract：:Retinoic acid (RA) plays key roles in cell differentiation and growth arrest by activating nuclear RA receptors (RARs) (α, β and γ), which are ligand-dependent transcription factors. RARs are also phosphorylated in response to RA. Here, we investigated the in vivo relevance of the phosphorylation of RARs during RA-ind...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.145979
更新日期：2014-05-01 00:00:00
abstract：:Integrins are implicated in cell adhesion, migration and homeostasis. An important feature is their ability to adopt different affinity states that can be regulated by a variety of intra- and extracellular factors. To study affinity modulation of the integrin ectodomain by extracellular factors, we produced a soluble ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-04-01 00:00:00
abstract：:Ferlin proteins mediate membrane-fusion events in response to Ca(2+). Myoferlin, a member of the ferlin family, is required for normal muscle development, during which it mediates myoblast fusion. We isolated both damaged and intact myofibers from a mouse model of muscular dystrophy using laser-capture microdissection...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.065375
更新日期：2010-07-15 00:00:00
abstract：:Microtubule-associated protein 2 (MAP2) is an abundant neuron-specific protein that binds to microtubules through a domain near its carboxyl terminus that contains either three or four similar repeats of a 31 amino acid motif. When expressed in non-neuronal cells by transfection MAP2 stabilises microtubules and induce...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
abstract：:Madin-Darby canine kidney cells (MDCK) were transfected with a cDNA encoding the glycosyl-phosphatidylinositol (GPI)-anchored protein mouse Thy-1 in order to study the steady-state surface distribution of exogenous and endogenous GPI-linked proteins. Immunofluorescence of transfected cells grown on collagen-coated cov...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1990-05-01 00:00:00
abstract：:5'AMP nucleotidase activity was localized by electron microscopy in Dictyostelium discoideum during cell differentiation. In addition, the activity was assayed by micro enzymic methods in sections dissected from specific cellular regions of lyophilized individuals. The results of the 2 procedures were in agreement, de...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1980-10-01 00:00:00
abstract：:The type II transmembrane protein CD98, best known as the heavy chain of the heterodimeric amino acid transporters (HAT), is required for the surface expression and basolateral localization of this transporter complex in polarized epithelial cells. CD98 also interacts with beta1 integrins resulting in an increase in t...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01674
更新日期：2005-03-01 00:00:00
abstract：:Electrical synapses (gap junctions) rapidly transmit signals between neurons and are composed of connexins. In neurons, connexin36 (Cx36) is the most abundant isoform; however, the mechanisms underlying formation of Cx36-containing electrical synapses are unknown. We focus on homocellular and heterocellular gap juncti...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.133066
更新日期：2014-03-15 00:00:00
abstract：:In the eukaryotic cell, a protein quality control process termed endoplasmic reticulum-associated degradation (ERAD) rids the ER of aberrant proteins and unassembled components of protein complexes that fail to reach a transport-competent state. To identify novel genes required for ERAD, we devised a rapid immunoassay...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.00439
更新日期：2003-06-01 00:00:00
abstract：:The establishment of a tissue-culture system for epithelial cells derived from human foetal pancreas has recently been reported. Further analyses have now been made on these cells in vitro, together with parallel investigation of the distribution of different cell types within the intact foetal pancreas. Results suppo...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1988-05-01 00:00:00
abstract：:As chromosomes move polewards during anaphase in crane-fly spermatocytes, trailing arms commonly stretch backwards for a brief time, as if tethered to their partners. To test that notion, a laser microbeam was used to sever trailing arms and thereby release telomere-containing arm segments (called acentric fragments b...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2002-04-01 00:00:00
abstract：:Integrin alpha1beta1 is a collagen receptor predominantly found in mesenchymal tissues. Mice lacking this receptor are viable. We have previously suggested that alpha1beta1 might participate in the down-regulation of collagen gene expression observed in cells suspended inside collagen gels. The results presented here ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-02-01 00:00:00
abstract：:Mitochondria are dynamic organelles that undergo regulated fission and fusion events that are essential to maintain metabolic stability. We previously demonstrated that the mitochondrial fission GTPase DRP1 is a substrate for SUMOylation. To further understand how SUMOylation impacts mitochondrial function, we searche...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.03418
更新日期：2007-04-01 00:00:00
abstract：:The cell wall of 24-h zygotes of Fucus serratus is composed of 3 layers--an inner fibrillar layer (sulphated fucan), an outer fibrillar layer (alginic aicd/cellulose) and an exterior amorphous layer (sulphated fucan, alginic acid). The 2 layers containing sulphated fucan are preferentially thickened at the rhizoid pol...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1978-08-01 00:00:00
abstract：:In some individuals with autosomal dominant isolated growth hormone deficiency, one copy of growth hormone lacks amino acids 32-71 and is severely misfolded. We transfected COS7 cells with either wild-type human growth hormone or Delta 32-71 growth hormone and investigated subcellular localization of growth hormone an...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2001-10-01 00:00:00
abstract：:Mammalian Staufen2 (Stau2) is involved in mRNA transport in neurons. Here, we report that Stau2 is a double-stranded RNA-binding protein that is mainly expressed in the brain. We show that Stau2 is found in the somatodendritic compartment of neurons. In dendrites, Stau2 is aligned on individual tracts and colocalizes ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2002-08-15 00:00:00
abstract：:The tandemly organised ribosomal DNA (rDNA) repeats are transcribed by a dedicated RNA polymerase in a specialised nuclear compartment, the nucleolus. There appears to be an intimate link between the maintenance of nucleolar structure and the presence of heterochromatic chromatin domains. This is particularly evident ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：2000-12-01 00:00:00
abstract：:The Schizosaccaromyces pombe protein Flp1p belongs to a conserved family of serine-threonine-phosphatases. The founding member of this family, Saccharomyces cerevisiae Cdc14p, is required for inactivation of mitotic CDKs and reversal of CDK mediated phosphorylation at the end of mitosis, thereby bringing about the M-G...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.01107
更新日期：2004-05-15 00:00:00
abstract：:The specification of organs, tissues and cell types results from cell fate restrictions enacted by nuclear transcription factors under the control of conserved signaling pathways. The progenitor epithelium of the Drosophila compound eye, the eye imaginal disc, is a premier model for the study of such processes. Early ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.237834
更新日期：2020-05-26 00:00:00
abstract：:Most secretory proteins travel through a well-documented conventional secretion pathway involving the endoplasmic reticulum (ER) and the Golgi complex. However, recently, it has been shown that a significant number of proteins reach the plasma membrane or extracellular space via unconventional routes. Unconventional p...
journal_title：Journal of cell science
pub_type： 杂志文章,评审
doi：10.1242/jcs.213686
更新日期：2018-06-25 00:00:00
abstract：:A tissue culture system for epithelial cells derived from male human foetal genital ducts has been established. The cells show morphological and biochemical characteristics of ductal epithelial cells, and can be passaged and maintained in culture for considerable periods of time. These cells will provide a suitable sy...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:Cell migration is essential for normal development and many pathological processes. Rho-family small GTPases play important roles in this event. In particular, Rac regulates lamellipodia formation at the leading edge during migration. The small GTPase RhoG activates Rac through its effector ELMO and the ELMO-binding p...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：10.1242/jcs.02720
更新日期：2006-01-01 00:00:00
abstract：:When malignant human cells are crossed with diploid human keratinocytes, malignancy, as defined by progressive growth in vivo, is suppressed so long as the hybrid cells continue to produce involucrin, a protein that characterizes terminal differentiation in the keratinocyte. When, on continued cultivation in vitro, th...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1987-04-01 00:00:00
abstract：:Adaptors are the membrane-binding components of clathrin-coated vesicles. The interaction of the trans-Golgi coat adaptor AP1 with membrane-associated proteins was analyzed by affinity chromatography. Proteins of 83 and 52 kDa bound specifically to the core domain of AP1 and showed no interaction with AP2 or other cla...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:The auto-catalytic activation of the cyclin-dependent kinase Cdc2 or MPF (M-phase promoting factor) is an irreversible process responsible for the entry into M phase. In Xenopus oocyte, a positive feed-back loop between Cdc2 kinase and its activating phosphatase Cdc25 allows the abrupt activation of MPF and the entry ...
journal_title：Journal of cell science
pub_type： 杂志文章
doi：
更新日期：1999-11-01 00:00:00
