Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

EGFRvIII uses intrinsic and extrinsic mechanisms to reduce glioma adhesion and increase migration.

ABSTRACT: A lack of biological markers has limited our ability to identify the invasive cells responsible for glioblastoma multiforme (GBM). To become migratory and invasive, cells must downregulate matrix adhesions, which could be a physical marker of invasive potential. We engineered murine astrocytes with common GBM mutations, e.g. Ink4a (Ink) or PTEN deletion and expressing a constitutively active EGF receptor truncation (EGFRvIII), to elucidate their effect on adhesion. While loss of Ink or PTEN did not affect adhesion, counterparts expressing EGFRvIII were significantly less adhesive. EGFRvIII reduced focal adhesion size and number, and these cells - with more labile adhesions - displayed enhanced migration. Regulation appears to depend not on physical receptor association to integrins but, rather, on the activity of the receptor kinase, resulting in transcriptional integrin repression. Interestingly, EGFRvIII intrinsic signals can be propagated by cytokine crosstalk to cells expressing wild-type EGFR, resulting in reduced adhesion and enhanced migration. These data identify potential intrinsic and extrinsic mechanisms that gliomas use to invade surrounding parenchyma.

SUBMITTER: Banisadr A

PROVIDER: S-EPMC7774888 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Intrinsic and extrinsic mechanisms regulating satellite cell function.

Project description:Muscle stem cells, termed satellite cells, are crucial for skeletal muscle growth and regeneration. In healthy adult muscle, satellite cells are quiescent but poised for activation. During muscle regeneration, activated satellite cells transiently re-enter the cell cycle to proliferate and subsequently exit the cell cycle to differentiate or self-renew. Recent studies have demonstrated that satellite cells are heterogeneous and that subpopulations of satellite stem cells are able to perform asymmetric divisions to generate myogenic progenitors or symmetric divisions to expand the satellite cell pool. Thus, a complex balance between extrinsic cues and intrinsic regulatory mechanisms is needed to tightly control satellite cell cycle progression and cell fate determination. Defects in satellite cell regulation or in their niche, as observed in degenerative conditions such as aging, can impair muscle regeneration. Here, we review recent discoveries of the intrinsic and extrinsic factors that regulate satellite cell behaviour in regenerating and degenerating muscles.

| S-EPMC4419274 | biostudies-literature

Cell-intrinsic and -extrinsic mechanisms promote cell-type-specific cytokinetic diversity.

Project description:Cytokinesis, the physical division of one cell into two, is powered by constriction of an actomyosin contractile ring. It has long been assumed that all animal cells divide by a similar molecular mechanism, but growing evidence suggests that cytokinetic regulation in individual cell types has more variation than previously realized. In the four-cell Caenorhabditis elegans embryo, each blastomere has a distinct cell fate, specified by conserved pathways. Using fast-acting temperature-sensitive mutants and acute drug treatment, we identified cell-type-specific variation in the cytokinetic requirement for a robust forminCYK-1-dependent filamentous-actin (F-actin) cytoskeleton. In one cell (P2), this cytokinetic variation is cell-intrinsically regulated, whereas in another cell (EMS) this variation is cell-extrinsically regulated, dependent on both SrcSRC-1 signaling and direct contact with its neighbor cell, P2. Thus, both cell-intrinsic and -extrinsic mechanisms control cytokinetic variation in individual cell types and can protect against division failure when the contractile ring is weakened.

| S-EPMC6054530 | biostudies-literature

Epidermal growth factor-induced enhancement of glioblastoma cell migration in 3D arises from an intrinsic increase in speed but an extrinsic matrix- and proteolysis-dependent increase in persistence.

Project description:Epidermal growth factor (EGF) receptor-mediated cell migration plays a vital role in invasion of many tumor types. EGF receptor ligands increase invasiveness in vivo, but it remains unclear how consequent effects on intrinsic cell motility behavior versus effects on extrinsic matrix properties integrate to result in net increase of translational speed and/or directional persistence of migration in a 3D environment. Understanding this convolution is important for therapeutic targeting of tumor invasion, as key regulatory pathways for intrinsic versus extrinsic effects may not be coincident. Accordingly, we have undertaken a quantitative single-cell imaging study of glioblastoma cell movement in 3D matrices and on 2D substrata across a range of collagen densities with systematic variation of protease-mediated matrix degradation. In 3D, EGF induced a mild increase in cell speed and a strong increase in directional persistence, the latter depending heavily on matrix density and EGF-stimulated protease activity. In contrast, in 2D, EGF induced a similarly mild increase in speed but conversely a decrease in directional persistence (both independent of protease activity). Thus, the EGF-enhanced 3D tumor cell migration results only partially from cell-intrinsic effects, with override of cell-intrinsic persistence decrease by protease-mediated cell-extrinsic reduction of matrix steric hindrance.

| S-EPMC2555959 | biostudies-literature

SHP2 blockade enhances anti-tumor immunity via tumor cell intrinsic and extrinsic mechanisms.

Project description:SHP2 is a ubiquitous tyrosine phosphatase involved in regulating both tumor and immune cell signaling. In this study, we discovered a novel immune modulatory function of SHP2. Targeting this protein with allosteric SHP2 inhibitors promoted anti-tumor immunity, including enhancing T cell cytotoxic function and immune-mediated tumor regression. Knockout of SHP2 using CRISPR/Cas9 gene editing showed that targeting SHP2 in cancer cells contributes to this immune response. Inhibition of SHP2 activity augmented tumor intrinsic IFNγ signaling resulting in enhanced chemoattractant cytokine release and cytotoxic T cell recruitment, as well as increased expression of MHC Class I and PD-L1 on the cancer cell surface. Furthermore, SHP2 inhibition diminished the differentiation and inhibitory function of immune suppressive myeloid cells in the tumor microenvironment. SHP2 inhibition enhanced responses to anti-PD-1 blockade in syngeneic mouse models. Overall, our study reveals novel functions of SHP2 in tumor immunity and proposes that targeting SHP2 is a promising strategy for cancer immunotherapy.

| S-EPMC7809281 | biostudies-literature

Multicompartment cell-based modeling of confined migration: regulation by cell intrinsic and extrinsic factors.

Project description:Though cell and nuclear deformability are expected to influence efficiency of confined migration, their individual and collective influence on migration efficiency remains incompletely understood. In addition to cell intrinsic properties, the relevance of cell extrinsic factors on confined migration, if any, has not been adequately explored. Here we address these questions using a statistical mechanics-based stochastic modeling approach where cell/nuclear dimensions and their deformability are explicitly taken into consideration. In addition to demonstrating the importance of cell softness in sustaining confined migration, our results suggest that dynamic tuning of cell and nuclear properties at different stages of migration is essential for maximizing migration efficiency. Our simulations also implicate confinement shape and confinement history as two important cell extrinsic regulators of cell invasiveness. Together, our findings illustrate the strength of a multicompartment model in dissecting the contributions of multiple factors that collectively influence confined cell migration.

| S-EPMC6080655 | biostudies-literature

Extrinsic activin signaling cooperates with an intrinsic temporal program to increase mushroom body neuronal diversity.

Project description:Temporal patterning of neural progenitors leads to the sequential production of diverse neurons. To understand how extrinsic cues influence intrinsic temporal programs, we studied Drosophila mushroom body progenitors (neuroblasts) that sequentially produce only three neuronal types: ?, then ?'?', followed by ??. Opposing gradients of two RNA-binding proteins Imp and Syp comprise the intrinsic temporal program. Extrinsic activin signaling regulates the production of ?'?' neurons but whether it affects the intrinsic temporal program was not known. We show that the activin ligand Myoglianin from glia regulates the temporal factor Imp in mushroom body neuroblasts. Neuroblasts missing the activin receptor Baboon have a delayed intrinsic program as Imp is higher than normal during the ?'?' temporal window, causing the loss of ?'?' neurons, a decrease in ?? neurons, and a likely increase in ? neurons, without affecting the overall number of neurons produced. Our results illustrate that an extrinsic cue modifies an intrinsic temporal program to increase neuronal diversity.

| S-EPMC7365662 | biostudies-literature

Scribble loss promotes pancreatic cancer development through intrinsic and extrinsic mechanisms

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-07-17 | GSE243939 | GEO

The moth specialist spider <i>Cyrtarachne akirai</i> uses prey scales to increase adhesion.

Project description:Contaminants decrease adhesive strength by interfering with substrate contact. Spider webs adhering to moths present an ideal model to investigate how natural adhesives overcome contamination because moths' sacrificial layer of scales rubs off on sticky silk, facilitating escape. However, Cyrtarachninae spiders have evolved gluey capture threads that adhere well to moths. Cyrtarachne capture threads contain large glue droplets oversaturated with water, readily flowing but also prone to drying out. Here, we compare the spreading and adhesion of Cyrtarachne akirai glue on intact mothwings, denuded cuticle and glass to the glue of a common orb-weaving spider, Larinioides cornutus, to understand how C. akirai glue overcomes dirty surfaces. Videos show that C. akirai's glue spreading accelerates along the underlying moth cuticle after the glue seeps beneath the moth scales-not seen on denuded cuticle or hydrophilic glass. Larinioides cornutus glue droplets failed to penetrate the moth scales, their force of adhesion thus limited by the strength of attachment of scales to the cuticle. The large size and low viscosity of C. akirai glue droplets function together to use the three-dimensional topography of the moth's scales against itself via capillary forces. Infrared spectroscopy shows C. akirai glue droplets readily lose free-flowing water. We hypothesize that this loss of water leads to increased viscosity during spreading, increasing cohesive forces during pull-off. This glue's two-phase behaviour shows how natural selection can leverage a defensive specialization of prey against themselves and highlights a new design principle for synthetic adhesives for adhering to troublesome surfaces.

| S-EPMC7014792 | biostudies-literature

Intrinsic and extrinsic mechanisms cooperate to ensure efficient termination of RNAPIII transcription.

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-07-13 | GSE174738 | GEO

<i>Drosophila</i> Fezf coordinates laminar-specific connectivity through cell-intrinsic and cell-extrinsic mechanisms.

Project description:Laminar arrangement of neural connections is a fundamental feature of neural circuit organization. Identifying mechanisms that coordinate neural connections within correct layers is thus vital for understanding how neural circuits are assembled. In the medulla of the Drosophila visual system neurons form connections within ten parallel layers. The M3 layer receives input from two neuron types that sequentially innervate M3 during development. Here we show that M3-specific innervation by both neurons is coordinated by Drosophila Fezf (dFezf), a conserved transcription factor that is selectively expressed by the earlier targeting input neuron. In this cell, dFezf instructs layer specificity and activates the expression of a secreted molecule (Netrin) that regulates the layer specificity of the other input neuron. We propose that employment of transcriptional modules that cell-intrinsically target neurons to specific layers, and cell-extrinsically recruit other neurons is a general mechanism for building layered networks of neural connections.

| S-EPMC5854465 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data