scholarly journals β-Catenin Signalling in Glioblastoma Multiforme and Glioma-Initiating Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Mireia Nager ◽  
Deepshikha Bhardwaj ◽  
Carles Cantí ◽  
Loreta Medina ◽  
Pere Nogués ◽  
...  

Glioblastoma multiforme (GBM) is a commonly occurring brain tumor with a poor prognosis. GBM can develop both “de novo” or evolve from a previous astrocytoma and is characterized by high proliferation and infiltration into the surrounding tissue. Following treatment (surgery, radiotherapy, and chemotherapy), tumors often reappear. Glioma-initiating cells (GICs) have been identified in GBM and are thought to be responsible for tumors initiation, their continued growth, and recurrence. β-catenin, a component of the cell-cell adhesion complex and of the canonical Wnt pathway, regulates proliferation, adhesion, and migration in different cell types. β-catenin and components of the Wnt canonical pathway are commonly overexpressed in GBM. Here, we review previous work on the role of Wnt/β-catenin signalling in glioma initiation, proliferation, and invasion. Understanding the molecular mechanisms regulating GIC biology and glioma progression may help in identifying novel therapeutic targets for GBM treatment.

2021 ◽  
Vol 22 (4) ◽  
pp. 2194
Author(s):  
Yi-Zhen Wang ◽  
Ebenezeri Erasto Ngowi ◽  
Di Wang ◽  
Hui-Wen Qi ◽  
Mi-Rong Jing ◽  
...  

Hydrogen sulfide (H2S) has long been considered as a toxic gas, but as research progressed, the idea has been updated and it has now been shown to have potent protective effects at reasonable concentrations. H2S is an endogenous gas signaling molecule in mammals and is produced by specific enzymes in different cell types. An increasing number of studies indicate that H2S plays an important role in cardiovascular homeostasis, and in most cases, H2S has been reported to be downregulated in cardiovascular diseases (CVDs). Similarly, in preclinical studies, H2S has been shown to prevent CVDs and improve heart function after heart failure. Recently, many H2S donors have been synthesized and tested in cellular and animal models. Moreover, numerous molecular mechanisms have been proposed to demonstrate the effects of these donors. In this review, we will provide an update on the role of H2S in cardiovascular activities and its involvement in pathological states, with a special focus on the roles of exogenous H2S in cardiac protection.


2009 ◽  
Vol 37 (6) ◽  
pp. 1171-1178 ◽  
Author(s):  
Ian C. Zachary ◽  
Paul Frankel ◽  
Ian M. Evans ◽  
Caroline Pellet-Many

NRPs (neuropilins) are receptors for class 3 semaphorins, polypeptides essential for axonal guidance, and for members of the VEGF (vascular endothelial growth factor) family of angiogenic cytokines. While mutant mouse studies show that NRP1 is essential for neuronal and cardiovascular development, little is known concerning the molecular mechanisms through which NRPs mediate the functions of their ligands in different cell types. NRP1 forms complexes with its co-receptors and is required for optimal function, but NRPs lack a clearly defined signalling domain and the role of NRP1 in receptor signalling and the function of the NRP1 cytosolic domain are unclear. Growing evidence indicates, however, that NRP1 plays a selective role in signalling at least in part via its C-terminal domain and interaction with intracellular binding partners.


2011 ◽  
Vol 22 (22) ◽  
pp. 4302-4311 ◽  
Author(s):  
Miguel A. Moreno-Mateos ◽  
Águeda G. Espina ◽  
Belén Torres ◽  
María M. Gámez del Estal ◽  
Ana Romero-Franco ◽  
...  

Pituitary tumor transforming gene 1 (PTTG1), also known as securin, has been implicated in many biological functions, including inhibition of sister chromatid separation, DNA repair, organ development, and regulation of the expression and secretion of angiogenic and metastatic factors. Although most of these functions of securin seem to depend on the localization of PTTG1 in the nucleus of the cell, a fraction of the protein has been also detected in the cytoplasm. Here we demonstrate that, in different cell types, a portion of cytoplasmic PTTG1 is associated with the cis face of the Golgi apparatus and that this localization depends on PTTG1 phosphorylation status. In this organelle, PTTG1 forms a complex with proteins involved in microtubule nucleation, including GM130, AKAP450, and γ-tubulin. RNA interference–mediated depletion of PTTG1 produces a delay in centrosomal and noncentrosomal microtubule nucleation. Cells lacking PTTG1 show severe defects in both cell polarization and migration in wound-healing assays. To our knowledge, this is the first study reporting the role of PTTG1 in microtubule nucleation and cell polarization, two processes directly involved in cell migration. We believe that these findings will contribute to understanding the mechanisms underlying PTTG1-mediated biological functions.


Acta Naturae ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 79-86 ◽  
Author(s):  
P. V. Elizar’ev ◽  
D. V. Lomaev ◽  
D. A. Chetverina ◽  
P. G. Georgiev ◽  
M. M. Erokhin

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.


Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1074
Author(s):  
Giuseppina Divisato ◽  
Silvia Piscitelli ◽  
Mariantonietta Elia ◽  
Emanuela Cascone ◽  
Silvia Parisi

Embryonic stem cells (ESCs) have the extraordinary properties to indefinitely proliferate and self-renew in culture to produce different cell progeny through differentiation. This latter process recapitulates embryonic development and requires rounds of the epithelial–mesenchymal transition (EMT). EMT is characterized by the loss of the epithelial features and the acquisition of the typical phenotype of the mesenchymal cells. In pathological conditions, EMT can confer stemness or stem-like phenotypes, playing a role in the tumorigenic process. Cancer stem cells (CSCs) represent a subpopulation, found in the tumor tissues, with stem-like properties such as uncontrolled proliferation, self-renewal, and ability to differentiate into different cell types. ESCs and CSCs share numerous features (pluripotency, self-renewal, expression of stemness genes, and acquisition of epithelial–mesenchymal features), and most of them are under the control of microRNAs (miRNAs). These small molecules have relevant roles during both embryogenesis and cancer development. The aim of this review was to recapitulate molecular mechanisms shared by ESCs and CSCs, with a special focus on the recently identified classes of microRNAs (noncanonical miRNAs, mirtrons, isomiRs, and competitive endogenous miRNAs) and their complex functions during embryogenesis and cancer development.


Biomolecules ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 349
Author(s):  
Nausika Betriu ◽  
Juan Bertran-Mas ◽  
Anna Andreeva ◽  
Carlos E. Semino

Pancreatic Ductal Adenocarcinoma (PDAC) is a fatal disease with poor prognosis because patients rarely express symptoms in initial stages, which prevents early detection and diagnosis. Syndecans, a subfamily of proteoglycans, are involved in many physiological processes including cell proliferation, adhesion, and migration. Syndecans are physiologically found in many cell types and their interactions with other macromolecules enhance many pathways. In particular, extracellular matrix components, growth factors, and integrins collect the majority of syndecans associations acting as biochemical, physical, and mechanical transducers. Syndecans are transmembrane glycoproteins, but occasionally their extracellular domain can be released from the cell surface by the action of matrix metalloproteinases, converting them into soluble molecules that are capable of binding distant molecules such as extracellular matrix (ECM) components, growth factor receptors, and integrins from other cells. In this review, we explore the role of syndecans in tumorigenesis as well as their potential as therapeutic targets. Finally, this work reviews the contribution of syndecan-1 and syndecan-2 in PDAC progression and illustrates its potential to be targeted in future treatments for this devastating disease.


2021 ◽  
Vol 21 ◽  
Author(s):  
Tahereh Zadeh Mehrizi

: Today, Platelets and platelet-derived nanoparticles and microparticles have found many applications in nanomedical technology. The results of our review study show that no article has been published in this field to review the current status of applications of these platelet derivatives so far. Therefore, in present study, our goal is to compare the applications of platelet derivatives and review their latest status between 2010 and 2020 to present the latest findings to researchers. A very interesting point about the role of platelet derivatives is the presence of molecules on their surface which makes them capable of hiding from the immune system, reaching different target cells, and specifically attaching to different cell types. According to the results of this study, most of their applications include drug delivery, diagnosis of various diseases, and tissue engineering. However, their application in drug delivery is limited due to heterogeneity, large size, and the possibility of interference with cellular pathways in microparticles derived from other cells. On the other hand, platelet nanoparticles are more controllable and have been widely used for drug delivery in treatment of cancer, atherosclerosis, thrombosis, infectious diseases, repair of damaged tissue, and photothermal therapy. The results of this study show that platelet nanoparticles are more controllable than platelet microparticles and have a higher potential for use in medicine.


Development ◽  
1973 ◽  
Vol 30 (2) ◽  
pp. 499-509
Author(s):  
Janet E. Hornby

Cell suspensions were prepared from the kidney, liver and heart of chick embryos of 5 or 8 days of incubation, and from the limb-buds of chick embryos of 5, 6, 7, 8 or 9 days of incubation. When these suspensions were aggregated under laminar shear in a Couette viscometer or random motion in a reciprocating shaker they obeyed the theoretical relationships derived for flocculating lyophobic sols. The values of the collision efficiency found for the different cell types under given conditions were used to calculate the force of interaction between cells of each type. The force of interaction ranged between 9 × 10−11 N (8-day heart) and 3 × 10−9 N (8-day liver). The forces of interaction between cells appear to be responsible for aligning the membranes of adjacent cells with a 10–20 nm gap. It is possible to arrange the cell types in a hierarchy based on the forces of interaction between them. The possible role of these forces in cell specificity is considered.


Author(s):  
Richard A. Seidu ◽  
Min Wu ◽  
Zhaoliang Su ◽  
Huaxi Xu

Gliomas represent 60% of primary intracranial brain tumors and 80% of all malignant types, with highest morbidity and mortality worldwide. Although glioma has been extensively studied, the molecular mechanisms underlying its pathology remain poorly understood. Clarification of the molecular mechanisms involved in their development and/or treatment resistance is highly required. High mobility group box 1 protein (HMGB1) is a nuclear protein that can also act as an extracellular trigger of inflammation, proliferation and migration, through receptor for advanced glycation end products and toll like receptors in a number of cancers including gliomas. It is known that excessive release of HMGB1 in cancer leads to unlimited replicative potential, ability to develop blood vessels (angiogenesis), evasion of programmed cell death (apoptosis), self-sufficiency in growth signals, insensitivity to inhibitors of growth, inflammation, tissue invasion and metastasis. In this review we explore the mechanisms by which HMGB1 regulates apoptosis and autophagy in glioma. We also looked at how HMGB1 mediates glioma regression and promotes angiogenesis as well as possible signaling pathways with an attempt to provide potential therapeutic targets for the treatment of glioma.


2017 ◽  
Vol 216 (10) ◽  
pp. 3405-3422 ◽  
Author(s):  
Vasja Urbančič ◽  
Richard Butler ◽  
Benjamin Richier ◽  
Manuel Peter ◽  
Julia Mason ◽  
...  

Filopodia have important sensory and mechanical roles in motile cells. The recruitment of actin regulators, such as ENA/VASP proteins, to sites of protrusion underlies diverse molecular mechanisms of filopodia formation and extension. We developed Filopodyan (filopodia dynamics analysis) in Fiji and R to measure fluorescence in filopodia and at their tips and bases concurrently with their morphological and dynamic properties. Filopodyan supports high-throughput phenotype characterization as well as detailed interactive editing of filopodia reconstructions through an intuitive graphical user interface. Our highly customizable pipeline is widely applicable, capable of detecting filopodia in four different cell types in vitro and in vivo. We use Filopodyan to quantify the recruitment of ENA and VASP preceding filopodia formation in neuronal growth cones, and uncover a molecular heterogeneity whereby different filopodia display markedly different responses to changes in the accumulation of ENA and VASP fluorescence in their tips over time.


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