scholarly journals Insulin signaling mediates neurodegeneration in glioma

2020 ◽  
Author(s):  
Patricia Jarabo ◽  
Carmen de Pablo ◽  
Héctor Herranz ◽  
Francisco Antonio Martín ◽  
Sergio Casas-Tintó
Keyword(s):  
Insulin Signaling ◽  
Neuronal Degeneration ◽  
Tumour Progression ◽  
Cell Communication ◽  
Premature Death ◽  
Insulin Pathway ◽  
Communication Signals ◽  
Synapse Loss ◽  
Neurodegenerative Process ◽  
Mitochondrial Disruption

AbstractCell to cell communication facilitates tissue development and physiology. Under pathological conditions, brain tumors disrupt glia-neuron communication signals that in consequence, promote tumor expansion at the expense of surrounding healthy tissue. The glioblastoma is the most aggressive and frequent brain tumor. This type of glioma expands and infiltrates into the brain, causing neuronal degeneration and neurological decay, among other symptoms. Here we describe how the glioblastoma produce ImpL2, an antagonist of the insulin pathway, which is regulated by the microRNA miR-8. ImpL2 targets neighboring neurons and causes mitochondrial disruption as well as synapse loss, both early symptoms of neurodegeneration. Furthermore, glioblastoma progression requires insulin pathway attenuation in neurons. Restoration of neuronal insulin activity is sufficient to rescue the synapse loss and to delay the premature death caused by glioma. Therefore, signals from GB to neuron emerge as a potential field of study to prevent neurodegeneration and to develop anti-tumoral strategies.Significance StatementGlioblastoma (GB) is the most aggressive type of brain tumour and currently there is no cure or effective treatment. Patients course with neurological decay and previous data in animal models indicate that GB cause a neurodegenerative process. We describe here a molecule named ImpL2 that is produced by GB cells and impact on neighbouring neurons. ImpL2 is an antagonist of the insulin pathway and signaling reduction in neurons causes mitochondrial defects and synapse loss. These mechanisms underlying GB-induced neurodegeneration plays a central role in the premature death caused by this tumour. Restoration of insulin signaling in neurons prevents tumour progression and rescues the lethality caused by GB in Drosophila models.

scholarly journals Insulin signaling mediates neurodegeneration in glioma

2021 ◽  
Vol 4 (3) ◽  
pp. e202000693
Author(s):  
Patricia Jarabo ◽  
Carmen de Pablo ◽  
Héctor Herranz ◽  
Francisco Antonio Martín ◽  
Sergio Casas-Tintó
Keyword(s):  
Brain Tumors ◽  
Neuronal Degeneration ◽  
Cell Communication ◽  
Premature Death ◽  
Insulin Pathway ◽  
Communication Signals ◽  
Synapse Loss ◽  
Surrounding Healthy Tissue ◽  
Insulin Activity ◽  
Mitochondrial Disruption

Cell to cell communication facilitates tissue development and physiology. Under pathological conditions, brain tumors disrupt glia-neuron communication signals that in consequence, promote tumor expansion at the expense of surrounding healthy tissue. The glioblastoma is one of the most aggressive and frequent primary brain tumors. This type of glioma expands and infiltrates into the brain, causing neuronal degeneration and neurological decay, among other symptoms. Here, we describe in a Drosophila model how glioblastoma cells produce ImpL2, an antagonist of the insulin pathway, which targets neighboring neurons and causes mitochondrial disruption as well as synapse loss, both early symptoms of neurodegeneration. Furthermore, glioblastoma progression requires insulin pathway attenuation in neurons. Restoration of neuronal insulin activity is sufficient to rescue synapse loss and to delay the premature death caused by glioma. Therefore, signals from glioblastoma to neuron emerge as a potential field of study to prevent neurodegeneration and to develop anti-tumoral strategies.

The cis -2-dodecenoic acid (BDSF) quorum sensing system in Burkholderia cenocepacia

2022 ◽  
Author(s):  
Mingfang Wang ◽  
Xia Li ◽  
Shihao Song ◽  
Chaoyu Cui ◽  
Lian-Hui Zhang ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Xanthomonas Campestris ◽  
Cell Communication ◽  
Burkholderia Cenocepacia ◽  
Bacterial Cells ◽  
Communication Signals ◽  
Signal Perception ◽  
Sensing System ◽  
Diffusible Signal Factor

It has been demonstrated that quorum sensing (QS) is widely employed by bacterial cells to coordinately regulate various group behaviors. Diffusible signal factor (DSF)-type signals have emerged as a growing family of conserved cell-cell communication signals. In addition to the DSF signal initially identified in Xanthomonas campestris pv. campestris, B urkholderia d iffusible s ignal f actor (BDSF, cis -2-dodecenoic acid) has been recognized as a conserved DSF-type signal with specific characteristics in both signal perception and transduction from DSF signals. Here, we review the history and current progress of the research of this type of signal, especially focusing on its biosynthesis, signaling pathways, and biological functions. We also discuss and explore the huge potential of targeting this kind of QS system as a new therapeutic strategy to control bacterial infections and diseases.

scholarly journals Interspecies Communication in Holobionts by Non-Coding RNA Exchange

2020 ◽  
Vol 21 (7) ◽  
pp. 2333
Author(s):  
Ana Lúcia Leitão ◽  
Marina C. Costa ◽  
André F. Gabriel ◽  
Francisco J. Enguita
Keyword(s):  
Target Cell ◽  
Current Knowledge ◽  
Cell Communication ◽  
Special Focus ◽  
Interspecies Communication ◽  
Communication Signals ◽  
Non Coding Rna ◽  
Molecular Machinery ◽  
Non Coding Rnas

Complex organisms are associations of different cells that coexist and collaborate creating a living consortium, the holobiont. The relationships between the holobiont members are essential for proper homeostasis of the organisms, and they are founded on the establishment of complex inter-connections between all the cells. Non-coding RNAs are regulatory molecules that can also act as communication signals between cells, being involved in either homeostasis or dysbiosis of the holobionts. Eukaryotic and prokaryotic cells can transmit signals via non-coding RNAs while using specific extracellular conveyors that travel to the target cell and can be translated into a regulatory response by dedicated molecular machinery. Within holobionts, non-coding RNA regulatory signaling is involved in symbiotic and pathogenic relationships among the cells. This review analyzes current knowledge regarding the role of non-coding RNAs in cell-to-cell communication, with a special focus on the signaling between cells in multi-organism consortia.

scholarly journals Notch-Jagged signalling can give rise to clusters of cells exhibiting a hybrid epithelial/mesenchymal phenotype

2016 ◽  
Vol 13 (118) ◽  
pp. 20151106 ◽  
Author(s):  
Marcelo Boareto ◽  
Mohit Kumar Jolly ◽  
Aaron Goldman ◽  
Mika Pietilä ◽  
Sendurai A. Mani ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Tumour Progression ◽  
Cell Communication ◽  
Notch Signalling ◽  
Circulating Tumour Cells ◽  
Mesenchymal Phenotype ◽  
Mesenchymal Transition ◽  
Mesenchymal To Epithelial Transition ◽  
Key Players

Metastasis can involve repeated cycles of epithelial-to-mesenchymal transition (EMT) and its reverse mesenchymal-to-epithelial transition. Cells can also undergo partial transitions to attain a hybrid epithelial/mesenchymal (E/M) phenotype that allows the migration of adhering cells to form a cluster of circulating tumour cells. These clusters can be apoptosis-resistant and possess an increased metastatic propensity as compared to the cells that undergo a complete EMT (mesenchymal cells). Hence, identifying the key players that can regulate the formation and maintenance of such clusters may inform anti-metastasis strategies. Here, we devise a mechanism-based theoretical model that links cell–cell communication via Notch-Delta-Jagged signalling with the regulation of EMT. We demonstrate that while both Notch-Delta and Notch-Jagged signalling can induce EMT in a population of cells, only Jagged-dominated Notch signalling, but not Delta-dominated signalling, can lead to the formation of clusters containing hybrid E/M cells. Our results offer possible mechanistic insights into the role of Jagged in tumour progression, and offer a framework to investigate the effects of other microenvironmental signals during metastasis.

scholarly journals Loss of the golgin GM130 causes Golgi disruption, Purkinje neuron loss, and ataxia in mice

2016 ◽  
Vol 114 (2) ◽  
pp. 346-351 ◽  
Author(s):  
Chunyi Liu ◽  
Mei Mei ◽  
Qiuling Li ◽  
Peristera Roboti ◽  
Qianqian Pang ◽  
...  
Keyword(s):  
Golgi Apparatus ◽  
Purkinje Cell ◽  
Secretory Pathway ◽  
Neuronal Degeneration ◽  
Cell Loss ◽  
Cell Number ◽  
Causative Role ◽  
Neurodegenerative Process ◽  
And Function

The Golgi apparatus lies at the heart of the secretory pathway where it is required for secretory trafficking and cargo modification. Disruption of Golgi architecture and function has been widely observed in neurodegenerative disease, but whether Golgi dysfunction is causal with regard to the neurodegenerative process, or is simply a manifestation of neuronal death, remains unclear. Here we report that targeted loss of the golgin GM130 leads to a profound neurological phenotype in mice. Global KO of mouse GM130 results in developmental delay, severe ataxia, and postnatal death. We further show that selective deletion of GM130 in neurons causes fragmentation and defective positioning of the Golgi apparatus, impaired secretory trafficking, and dendritic atrophy in Purkinje cells. These cellular defects manifest as reduced cerebellar size and Purkinje cell number, leading to ataxia. Purkinje cell loss and ataxia first appear during postnatal development but progressively worsen with age. Our data therefore indicate that targeted disruption of the mammalian Golgi apparatus and secretory traffic results in neuronal degeneration in vivo, supporting the view that Golgi dysfunction can play a causative role in neurodegeneration.

scholarly journals Cooperation of partially-transformed clones: an invisible force behind the early stages of carcinogenesis

2018 ◽  
Author(s):  
Alessandro Esposito
Keyword(s):  
Tumour Progression ◽  
Three Dimensional ◽  
Cell Communication ◽  
Significant Heterogeneity ◽  
Early Stages ◽  
Dna Mutations ◽  
A Cell ◽  
Mechanisms Of Carcinogenesis ◽  
Fundamental Forces ◽  
Mutational Process

AbstractMost tumours exhibit significant heterogeneity and are best described as communities of cellular populations competing for resources. Growing experimental evidence also suggests, however, that cooperation between cancer clones is important as well for the maintenance of tumour heterogeneity and tumour progression. However, a role for cell communication during the earliest steps in oncogenesis is not well characterised despite its vital importance in normal tissue and clinically manifest tumours. By modelling the interaction between the mutational process and cell-to-cell communication in three-dimensional tissue architecture, we show that non-cell-autonomous mechanisms of carcinogenesis could support and accelerate pre-cancerous clonal expansion through the cooperation of different, non- or partially- transformed mutants. We predict the existence of a ‘cell-autonomous time-horizon’, a time before which cooperation between cell-to-cell communication and DNA mutations might be one of the most fundamental forces shaping the early stages of oncogenesis. The understanding of this process could shed new light on the mechanisms leading to clinically manifest cancers.

scholarly journals Cytonemes in Tumourigenesis

2019 ◽  
Author(s):  
Marta Portela
Keyword(s):  
Cancer Progression ◽  
Tumour Progression ◽  
Cell Signalling ◽  
Cell Communication ◽  
Cell Types ◽  
Wing Disc ◽  
Genetic Ablation ◽  
The Past ◽  
Tumoral Cell ◽  
To Receive

Increasing evidence during the past two decades shows that cells interconnect and communicate through cytonemes. These cytoskeleton-driven extensions of specialized membrane territories have emerged as a novel alternative for cell to cell communication that are involved in development, physiology, and disease. Several recent studies have shown that signalling pathways mediated by cytonemes during development, are essential for certain tumoral cell types progression. In Drosophila wing disc EGFR and RET tumour models, cytoneme formation is required to receive signals from the neighbouring cells. Genetic ablation of cytonemes prevents tumour progression, restores apico-basal polarity, and improves survival. Furthermore, cytonemes in the Drosophila glial cells are essential for glioblastoma progression as they alter Wg/Fz1 signalling between glia and neurons. Research on cytoneme formation, maintenance, and cell signalling mechanisms will help to better understand not only physiological developmental processes and tissue homeostasis but also cancer progression.

scholarly journals iTALK: an R Package to Characterize and Illustrate Intercellular Communication

2019 ◽  
Author(s):  
Yuanxin Wang ◽  
Ruiping Wang ◽  
Shaojun Zhang ◽  
Shumei Song ◽  
Changying Jiang ◽  
...  
Keyword(s):  
Intercellular Communication ◽  
Cell Communication ◽  
R Package ◽  
Therapy Resistance ◽  
Computational Approach ◽  
Sequencing Data ◽  
Communication Signals ◽  
Cellular Processes ◽  
Wide Range ◽  
Single Cell Rna Sequencing

ABSTRACTCrosstalk between tumor cells and other cells within the tumor microenvironment (TME) plays a crucial role in tumor progression, metastases, and therapy resistance. We present iTALK, a computational approach to characterize and illustrate intercellular communication signals in the multicellular tumor ecosystem using single-cell RNA sequencing data. iTALK can in principle be used to dissect the complexity, diversity, and dynamics of cell-cell communication from a wide range of cellular processes.

scholarly journals In Silico and In Vitro Analysis of lncRNA XIST Reveals a Panel of Possible Lung Cancer Regulators and a Five-Gene Diagnostic Signature

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3499
Author(s):  
Periklis Katopodis ◽  
Qiduo Dong ◽  
Heerni Halai ◽  
Cristian I. Fratila ◽  
Andreas Polychronis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Lines ◽  
In Silico ◽  
Cell Biology ◽  
Tumour Progression ◽  
Cell Communication ◽  
Nucleic Acid Metabolism ◽  
Rna Seq ◽  
Diagnostic Potential

Long non-coding RNAs (lncRNAs) perform a wide functional repertoire of roles in cell biology, ranging from RNA editing to gene regulation, as well as tumour genesis and tumour progression. The lncRNA X-inactive specific transcript (XIST) is involved in the aetiopathogenesis of non-small cell lung cancer (NSCLC). However, its role at the molecular level is not fully elucidated. The expression of XIST and co-regulated genes TSIX, hnRNPu, Bcl-2, and BRCA1 analyses in lung cancer (LC) and controls were performed in silico. Differentially expressed genes (DEGs) were determined using RNA-seq in H1975 and A549 NSCLC cell lines following siRNA for XIST. XIST exhibited sexual dimorphism, being up-regulated in females compared to males in both control and LC patient cohorts. RNA-seq revealed 944 and 751 DEGs for A549 and H1975 cell lines, respectively. These DEGs are involved in signal transduction, cell communication, energy pathways, and nucleic acid metabolism. XIST expression associated with TSIX, hnRNPu, Bcl-2, and BRCA1 provided a strong collective feature to discriminate between controls and LC, implying a diagnostic potential. There is a much more complex role for XIST in lung cancer. Further studies should concentrate on sex-specific changes and investigate the signalling pathways of the DEGs following silencing of this lncRNA.

Defining the expression, production, and signaling roles of specialized metabolites during Bacillus subtilis differentiation

2021 ◽  
Author(s):  
Alexi A. Schoenborn ◽  
Sarah M. Yannarell ◽  
E. Diane Wallace ◽  
Haley Clapper ◽  
Ilon C. Weinstein ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Biofilm Formation ◽  
Cell Communication ◽  
Signaling Molecules ◽  
Interspecies Interactions ◽  
Communication Signals ◽  
Specialized Metabolites ◽  
Growing Body ◽  
Antagonistic Potential ◽  
Cell Cell

Bacterial specialized (or secondary) metabolites are structurally diverse molecules that mediate intra- and interspecies interactions by altering growth and cellular physiology and differentiation. Bacillus subtilis , a Gram-positive model bacterium commonly used to study biofilm formation and sporulation, has the capacity to produce over ten specialized metabolites. Some of these B. subtilis specialized metabolites have been investigated for their role in facilitating cellular differentiation, only rarely has the behavior of multiple metabolites been simultaneously investigated. In this study, we explored the interconnectivity of differentiation (biofilm and sporulation) and specialized metabolites in B. subtilis . Specifically, we interrogated how development influences specialized metabolites and vice versa. Using the sporulation-inducing medium DSM, we found that the majority of the specialized metabolites examined are expressed and produced during biofilm formation and sporulation. Additionally, we found that six of these metabolites (surfactin, ComX, bacillibactin, bacilysin, subtilosin A, and plipastatin) are necessary signaling molecules for proper progression of B. subtilis differentiation. This study further supports the growing body of work demonstrating that specialized metabolites have essential physiological functions as cell-cell communication signals in bacteria. Importance/Significance Bacterially produced specialized metabolites are frequently studied for their potential use as antibiotics and antifungals. However, a growing body of work has suggested that the antagonistic potential of specialized metabolites is not their only function. Here, using Bacillus subtilis as our model bacterium, we demonstrated that developmental processes such as biofilm formation and sporulation are tightly linked with specialized metabolite gene expression and production. Additionally, under our differentiation-inducing conditions, six out of the nine specialized metabolites investigated behave as intraspecific signals that impact B. subtilis physiology and influence biofilm formation and sporulation. Our work supports the viewpoint that specialized metabolites have a clear role as cell-cell signaling molecules within differentiated populations of bacteria.

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