A new biomimetic assay reveals the temporal role of matrix stiffening in cancer cell invasion.

Abstract:

:Tumor initiation and growth is associated with significant changes in the surrounding tissue. During carcinoma progression, a global stiffening of the extracellular matrix is observed and is interpreted as a signature of aggressive invasive tumors. However, it is still unknown whether this increase in matrix rigidity promotes invasion and whether this effect is constant along the course of invasion. Here we have developed a biomimetic in vitro assay that enabled us to address the question of the importance of tissue rigidity in the chronology of tumor invasion. Using low concentrations of the sugar threose, we can effectively stiffen reconstituted collagen I matrices and control the stiffening in time with no direct effect on residing cells. Our findings demonstrate that, depending on the timing of its stiffening, the extracellular matrix could either inhibit or promote cancer cell invasion and subsequent metastasis: while matrix stiffening after the onset of invasion promotes cancer cell migration and tumor spreading, stiff matrices encapsulate the tumor at an early stage and prevent cancer cell invasion. Our study suggests that adding a temporal dimension in in vitro models to analyze biological processes in four dimensions is necessary to fully capture their complexity.

journal_name

Mol Biol Cell

authors

Staneva R,Burla F,Koenderink GH,Descroix S,Vignjevic DM,Attieh Y,Verhulsel M

doi

10.1091/mbc.E18-01-0068

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

2979-2988

issue

25

eissn

1059-1524

issn

1939-4586

journal_volume

29

pub_type

杂志文章
  • Calcineurin regulates cyclin D1 accumulation in growth-stimulated fibroblasts.

    abstract::Calcium (Ca(2+)) and calmodulin (CaM) are required for progression of mammalian cells from quiescence into S phase. In multiple cell types, cyclosporin A causes a G(1) cell cycle arrest, implicating the serine/threonine phosphatase calcineurin as one Ca(2+)/CaM-dependent enzyme required for G(1) transit. Here, we show...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-10-0730

    authors: Kahl CR,Means AR

    更新日期:2004-04-01 00:00:00

  • CDK-dependent phosphorylation of Mob2 is essential for hyphal development in Candida albicans.

    abstract::Nuclear Dbf2-related (NDR) protein kinases are essential components of regulatory pathways involved in cell morphogenesis, cell cycle control, and viability in eukaryotic cells. For their activity and function, these kinases require interaction with Mob proteins. However, little is known about how the Mob proteins are...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-03-0205

    authors: Gutiérrez-Escribano P,González-Novo A,Suárez MB,Li CR,Wang Y,de Aldana CR,Correa-Bordes J

    更新日期:2011-07-15 00:00:00

  • Plasma membrane organization is essential for balancing competing pseudopod- and uropod-promoting signals during neutrophil polarization and migration.

    abstract::Exposure of neutrophils to chemoattractant induces cell polarization and migration. These behaviors require the asymmetric activation of distinct signaling pathways and cytoskeletal elements in the protruding pseudopod at the front of cells and the retracting uropod at the rear. An important outstanding question is, h...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-04-0358

    authors: Bodin S,Welch MD

    更新日期:2005-12-01 00:00:00

  • Scientific societies fostering inclusivity through speaker diversity in annual meeting programming: a call to action.

    abstract::Scientific societies aiming to foster inclusion of scientists from underrepresented (UR) backgrounds among their membership often delegate primary responsibility for this goal to a diversity-focused committee. The National Science Foundation has funded the creation of the Alliance to Catalyze Change for Equity in STEM...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E20-06-0381

    authors: Segarra VA,Primus C,Unguez GA,Edwards A,Etson C,Flores SC,Fry C,Guillory AN,Ingram SL,Lawson M,McGee R,Paxson S,Phelan L,Suggs K,Vega LR,Vuong E,Havran JC,Leon A,Burton MD,Lujan JL,Ramirez-Alvarado M

    更新日期:2020-11-01 00:00:00

  • Direct inhibition of myosin II effectively blocks glioma invasion in the presence of multiple motogens.

    abstract::Anaplastic gliomas, the most common and malignant of primary brain tumors, frequently contain activating mutations and amplifications in promigratory signal transduction pathways. However, targeting these pathways with individual signal transduction inhibitors does not appreciably reduce tumor invasion, because these ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-01-0039

    authors: Ivkovic S,Beadle C,Noticewala S,Massey SC,Swanson KR,Toro LN,Bresnick AR,Canoll P,Rosenfeld SS

    更新日期:2012-02-01 00:00:00

  • Changes in organization of the endoplasmic reticulum during Xenopus oocyte maturation and activation.

    abstract::The organization of the endoplasmic reticulum (ER) in the cortex of Xenopus oocytes was investigated during maturation and activation using a green fluorescent protein chimera, immunofluorescence, and electron microscopy. Dense clusters of ER developed on the vegetal side (the side opposite the meiotic spindle) during...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.4.1103

    authors: Terasaki M,Runft LL,Hand AR

    更新日期:2001-04-01 00:00:00

  • HSP70-binding protein HSPBP1 regulates chaperone expression at a posttranslational level and is essential for spermatogenesis.

    abstract::Molecular chaperones play key roles during growth, development, and stress survival. The ability to induce chaperone expression enables cells to cope with the accumulation of nonnative proteins under stress and complete developmental processes with an increased requirement for chaperone assistance. Here we generate an...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-02-0742

    authors: Rogon C,Ulbricht A,Hesse M,Alberti S,Vijayaraj P,Best D,Adams IR,Magin TM,Fleischmann BK,Höhfeld J

    更新日期:2014-08-01 00:00:00

  • Reorganization of actin cytoskeleton by the phosphoinositide metabolite glycerophosphoinositol 4-phosphate.

    abstract::Glycerophosphoinositol 4-phosphate (GroPIns-4P) is a biologically active, water-soluble phospholipase A metabolite derived from phosphatidylinositol 4-phosphate, whose cellular concentrations have been reported to increase in Ras-transformed cells. It is therefore important to understand its biological activities. Her...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-04-0179

    authors: Mancini R,Piccolo E,Mariggio' S,Filippi BM,Iurisci C,Pertile P,Berrie CP,Corda D

    更新日期:2003-02-01 00:00:00

  • Delineation of glutamate pathways and secretory responses in pancreatic islets with β-cell-specific abrogation of the glutamate dehydrogenase.

    abstract::In pancreatic β-cells, glutamate dehydrogenase (GDH) modulates insulin secretion, although its function regarding specific secretagogues is unclear. This study investigated the role of GDH using a β-cell-specific GDH knockout mouse model, called βGlud1(-/-). The absence of GDH in islets isolated from βGlud1(-/-) mice ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-08-0676

    authors: Vetterli L,Carobbio S,Pournourmohammadi S,Martin-Del-Rio R,Skytt DM,Waagepetersen HS,Tamarit-Rodriguez J,Maechler P

    更新日期:2012-10-01 00:00:00

  • The catalytic activity of the Src family kinases is required to disrupt cadherin-dependent cell-cell contacts.

    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

    authors: Owens DW,McLean GW,Wyke AW,Paraskeva C,Parkinson EK,Frame MC,Brunton VG

    更新日期:2000-01-01 00:00:00

  • Transcriptome analysis of tetraploid cells identifies cyclin D2 as a facilitator of adaptation to genome doubling in the presence of p53.

    abstract::Tetraploidization, or genome doubling, is a prominent event in tumorigenesis, primarily because cell division in polyploid cells is error-prone and produces aneuploid cells. This study investigates changes in gene expression evoked in acute and adapted tetraploid cells and their effect on cell-cycle progression. Acute...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-05-0268

    authors: Potapova TA,Seidel CW,Box AC,Rancati G,Li R

    更新日期:2016-10-15 00:00:00

  • Cross talk between tetanus neurotoxin-insensitive vesicle-associated membrane protein-mediated transport and L1-mediated adhesion.

    abstract::The membrane-trafficking pathway mediated by tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP) in neurons is still unknown. We show herein that TI-VAMP expression is necessary for neurite outgrowth in PC12 cells and hippocampal neurons in culture. TI-VAMP interacts with plasma membrane and e...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-03-0147

    authors: Alberts P,Rudge R,Hinners I,Muzerelle A,Martinez-Arca S,Irinopoulou T,Marthiens V,Tooze S,Rathjen F,Gaspar P,Galli T

    更新日期:2003-10-01 00:00:00

  • Peroxisomal membrane proteins contain common Pex19p-binding sites that are an integral part of their targeting signals.

    abstract::Targeting of peroxisomal membrane proteins (PMPs) is a multistep process that requires not only recognition of PMPs in the cytosol but also their insertion into the peroxisomal membrane. As a consequence, targeting signals of PMPs (mPTS) are rather complex. A candidate protein for the PMP recognition event is Pex19p, ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-03-0188

    authors: Rottensteiner H,Kramer A,Lorenzen S,Stein K,Landgraf C,Volkmer-Engert R,Erdmann R

    更新日期:2004-07-01 00:00:00

  • Temporal regulation of cell polarity via the interaction of the Ras GTPase Rsr1 and the scaffold protein Bem1.

    abstract::The Cdc42 guanosine triphosphatase (GTPase) plays a central role in polarity development in species ranging from yeast to humans. In budding yeast, a specific growth site is selected in the G1 phase. Rsr1, a Ras GTPase, interacts with Cdc42 and its associated proteins to promote polarized growth at the proper bud site...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-02-0106

    authors: Miller KE,Lo WC,Chou CS,Park HO

    更新日期:2019-09-15 00:00:00

  • Two high-yield complementary methods to sort cell populations by their 2D or 3D migration speed.

    abstract::The potential to migrate is one of the most fundamental functions for various epithelial, mesenchymal, and immune cells. Image analysis of motile cell populations, both primary and cultured, typically reveals an intercellular variability in migration speeds. However, cell migration chromatography, the sorting of large...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E20-07-0466

    authors: Arora A,Niño JLG,Myaing MZ,Chia S,Arasi B,Ravasio A,Huang RY,Dasgupta R,Biro M,Viasnoff V

    更新日期:2020-12-01 00:00:00

  • Role of gelsolin in actin depolymerization of adherent human neutrophils.

    abstract::Human neutrophils generally function adherent to an extracellular matrix. We have previously reported that upon adhesion to laminin- or fibronectin-coated, but not uncoated, plastic there is a depolymerization of actin in neutrophils. This phenomenon was not affected by inhibitors of the more well-studied components o...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.8.1.121

    authors: Wang JS,Coburn JP,Tauber AI,Zaner KS

    更新日期:1997-01-01 00:00:00

  • Mutant rab8 Impairs docking and fusion of rhodopsin-bearing post-Golgi membranes and causes cell death of transgenic Xenopus rods.

    abstract::Rab8 is a GTPase involved in membrane trafficking. In photoreceptor cells, rab8 is proposed to participate in the late stages of delivery of rhodopsin-containing post-Golgi membranes to the plasma membrane near the base of the connecting cilium. To test the function of rab8 in vivo, we generated transgenic Xenopus lae...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.8.2341

    authors: Moritz OL,Tam BM,Hurd LL,Peränen J,Deretic D,Papermaster DS

    更新日期:2001-08-01 00:00:00

  • Ezrin regulates focal adhesion and invadopodia dynamics by altering calpain activity to promote breast cancer cell invasion.

    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...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-12-1584

    authors: Hoskin V,Szeto A,Ghaffari A,Greer PA,Côté GP,Elliott BE

    更新日期:2015-10-01 00:00:00

  • Distinct roles for the AAA ATPases NSF and p97 in the secretory pathway.

    abstract::NSF and p97 are related AAA proteins implicated in membrane trafficking and organelle biogenesis. p97 is also involved in pathways that lead to ubiquitin-dependent proteolysis, including ER-associated degradation (ERAD). In this study, we have used dominant interfering ATP-hydrolysis deficient mutants (NSF(E329Q) and ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-02-0097

    authors: Dalal S,Rosser MF,Cyr DM,Hanson PI

    更新日期:2004-02-01 00:00:00

  • Proteolytic processing and Ca2+-binding activity of dense-core vesicle polypeptides in Tetrahymena.

    abstract::Formation and discharge of dense-core secretory vesicles depend on controlled rearrangement of the core proteins during their assembly and dispersal. The ciliate Tetrahymena thermophila offers a simple system in which the mechanisms may be studied. Here we show that most of the core consists of a set of polypeptides d...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.9.2.497

    authors: Verbsky JW,Turkewitz AP

    更新日期:1998-02-01 00:00:00

  • Divergent roles of c-Src in controlling platelet-derived growth factor-dependent signaling in fibroblasts.

    abstract::The vast complexity of platelet-derived growth factor (PDGF)-induced downstream signaling pathways is well known, but the precise roles of critical players still elude us due to our lack of specific and temporal control over their activities. Accordingly, although Src family members are some of the better characterize...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-03-0263

    authors: Shah K,Vincent F

    更新日期:2005-11-01 00:00:00

  • MTG1 codes for a conserved protein required for mitochondrial translation.

    abstract::The MTG1 gene of Saccharomyces cerevisiae, corresponding to ORF YMR097c on chromosome XIII, codes for a mitochondrial protein essential for respiratory competence. A human homologue of Mtg1p capable of partially rescuing the respiratory deficiency of a yeast mtg1 mutant has also been localized in mitochondria. Mtg1p i...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-10-0636

    authors: Barrientos A,Korr D,Barwell KJ,Sjulsen C,Gajewski CD,Manfredi G,Ackerman S,Tzagoloff A

    更新日期:2003-06-01 00:00:00

  • Genetic mosaic analysis of a deleterious mitochondrial DNA mutation in Drosophila reveals novel aspects of mitochondrial regulation and function.

    abstract::Various human diseases are associated with mitochondrial DNA (mtDNA) mutations, but heteroplasmy—the coexistence of mutant and wild-type mtDNA—complicates their study. We previously isolated a temperature-lethal mtDNA mutation in Drosophila, mt:CoI(T300I), which affects the cytochrome c oxidase subunit I (CoI) locus. ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E14-11-1513

    authors: Chen Z,Qi Y,French S,Zhang G,Covian Garcia R,Balaban R,Xu H

    更新日期:2015-02-15 00:00:00

  • The mitochondrial Hsp70 chaperone Ssq1 facilitates Fe/S cluster transfer from Isu1 to Grx5 by complex formation.

    abstract::The mitochondrial Hsp70 chaperone Ssq1 plays a dedicated role in the maturation of iron-sulfur (Fe/S) proteins, an essential process of mitochondria. Similar to its bacterial orthologue HscA, Ssq1 binds to the scaffold protein Isu1, thereby facilitating dissociation of the newly synthesized Fe/S cluster on Isu1 and it...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E12-09-0644

    authors: Uzarska MA,Dutkiewicz R,Freibert SA,Lill R,Mühlenhoff U

    更新日期:2013-06-01 00:00:00

  • ATP-dependent membrane assembly of F-actin facilitates membrane fusion.

    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

    authors: Jahraus A,Egeberg M,Hinner B,Habermann A,Sackman E,Pralle A,Faulstich H,Rybin V,Defacque H,Griffiths G

    更新日期:2001-01-01 00:00:00

  • Echovirus 1 endocytosis into caveosomes requires lipid rafts, dynamin II, and signaling events.

    abstract::Binding of echovirus 1 (EV1, a nonenveloped RNA virus) to the alpha2beta1 integrin on the cell surface is followed by endocytic internalization of the virus together with the receptor. Here, video-enhanced live microscopy revealed the rapid uptake of fluorescently labeled EV1 into mobile, intracellular structures, pos...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e04-01-0070

    authors: Pietiäinen V,Marjomäki V,Upla P,Pelkmans L,Helenius A,Hyypiä T

    更新日期:2004-11-01 00:00:00

  • The hydrophobic core of the Sec61 translocon defines the hydrophobicity threshold for membrane integration.

    abstract::The Sec61 translocon mediates the translocation of proteins across the endoplasmic reticulum membrane and the lateral integration of transmembrane segments into the lipid bilayer. The structure of the idle translocon is closed by a lumenal plug domain and a hydrophobic constriction ring. To test the function of the ap...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e10-01-0060

    authors: Junne T,Kocik L,Spiess M

    更新日期:2010-05-15 00:00:00

  • Nse1-dependent recruitment of Smc5/6 to lesion-containing loci contributes to the repair defects of mutant complexes.

    abstract::Of the three structural maintenance of chromosomes (SMC) complexes, Smc5/6 remains the most poorly understood. Genetic studies have shown that Smc5/6 mutants are defective in homologous recombination (HR), and consistent with this, Smc5/6 is enriched at lesions. However, Smc5/6 is essential for viability, but HR is no...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-03-0272

    authors: Tapia-Alveal C,O'Connell MJ

    更新日期:2011-12-01 00:00:00

  • Organization of the yeast Golgi complex into at least four functionally distinct compartments.

    abstract::Pro-alpha-factor (pro-alphaf) is posttranslationally modified in the yeast Golgi complex by the addition of alpha1,6-, alpha1,2-, and alpha1,3-linked mannose to N-linked oligosaccharides and by a Kex2p-initiated proteolytic processing event. Previous work has indicated that the alpha1,6- and alpha1,3-mannosylation and...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.1.171

    authors: Brigance WT,Barlowe C,Graham TR

    更新日期:2000-01-01 00:00:00

  • Cysteine string protein functions directly in regulated exocytosis.

    abstract::Cysteine string protein (Csp) is essential for neurotransmitter release in Drosophila. It has been suggested that Csp functions by regulating the activity of presynaptic Ca2+ channels, thus controlling exocytosis. We have examined the effect of overexpressing Csp1 in PC12 cells, a neuroendocrine cell line. PC12 cell c...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.9.8.2259

    authors: Chamberlain LH,Burgoyne RD

    更新日期:1998-08-01 00:00:00