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https://www.readbyqxmd.com/read/28205624/the-small-molecule-auten-99-autophagy-enhancer-99-prevents-the-progression-of-neurodegenerative-symptoms
#1
Tibor Kovács, Viktor Billes, Marcell Komlós, Bernadette Hotzi, Anna Manzéger, Anna Tarnóci, Diána Papp, Fanni Szikszai, Janka Szinyákovics, Ákos Rácz, Béla Noszál, Szilvia Veszelka, Fruzsina R Walter, Mária A Deli, Laszlo Hackler, Robert Alfoldi, Orsolya Huzian, Laszlo G Puskas, Hanna Liliom, Krisztián Tárnok, Katalin Schlett, Adrienn Borsy, Ervin Welker, Attila L Kovács, Zsolt Pádár, Attila Erdős, Adam Legradi, Annamaria Bjelik, Károly Gulya, Balázs Gulyás, Tibor Vellai
Autophagy functions as a main route for the degradation of superfluous and damaged constituents of the cytoplasm. Defects in autophagy are implicated in the development of various age-dependent degenerative disorders such as cancer, neurodegeneration and tissue atrophy, and in accelerated aging. To promote basal levels of the process in pathological settings, we previously screened a small molecule library for novel autophagy-enhancing factors that inhibit the myotubularin-related phosphatase MTMR14/Jumpy, a negative regulator of autophagic membrane formation...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196804/nipped-a-regulates-intestinal-stem-cell-proliferation-in-drosophila
#2
Helen Marie Tauc, Alpaslan Tasdogan, Patrick Meyer, Petra Pandur
Adult stem cells uphold a delicate balance between quiescent and active states, a deregulation of which can lead to age-associated diseases such as cancer. In Drosophila, intestinal stem cell (ISC) proliferation is tightly regulated and mis-regulation is detrimental to intestinal homeostasis. Various factors are known to govern ISC behavior; however, transcriptional changes in ISCs during aging are still unclear. RNA sequencing of young and old ISCs newly identified Nipped-A, a subunit of histone acetyltransferase complexes, as a regulator of ISC proliferation that is upregulated in old ISCs...
February 15, 2017: Development
https://www.readbyqxmd.com/read/28196122/detrimental-elavl-1-hur-dependent-gsk3%C3%AE-mrna-stabilization-impairs-resolution-in-acute-respiratory-distress-syndrome
#3
Olivia Hoffman, Nana Burns, István Vadász, Holger K Eltzschig, Michael G Edwards, Christine U Vohwinkel
A hallmark of acute respiratory distress syndrome (ARDS) is accumulation of protein-rich edema in the distal airspaces and its removal is critical for patient survival. Previous studies have shown a detrimental role of Glycogen Synthase Kinase (GSK) 3β during ARDS via inhibition of alveolar epithelial protein transport. We hypothesized that post-transcriptional regulation of GSK3β could play a functional role in ARDS resolution. To address this hypothesis, we performed an in silico analysis to identify regulatory genes whose expression correlation to GSK3β messenger RNA utilizing two lung cancer cell line array datasets...
2017: PloS One
https://www.readbyqxmd.com/read/28188816/a-chemical-genomics-approach-to-drug-reprofiling-in-oncology-antipsychotic-drug-risperidone-as-a-potential-adenocarcinoma-treatment
#4
Suzanne J Dilly, Andrew J Clark, Andrew Marsh, Daniel A Mitchell, Ricky Cain, Colin W G Fishwick, Paul C Taylor
Drug reprofiling is emerging as an effective paradigm for discovery of cancer treatments. Herein, an antipsychotic drug is immobilised using the Magic Tag(®) chemical genomics tool and screened against a T7 bacteriophage displayed library of polypeptides from Drosophila melanogaster, as a whole genome model, to uncover an interaction with a section of 17-β-HSD10, a proposed prostate cancer target. A computational study and enzyme inhibition assay with full length human 17-β-HSD10 identifies risperidone as a drug reprofiling candidate...
February 8, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28178204/epidermal-growth-factor-pathway-signaling-in-drosophila-embryogenesis-tools-for-understanding-cancer
#5
REVIEW
Jay B Lusk, Vanessa Y M Lam, Nicholas S Tolwinski
EGF signaling is a well-known oncogenic pathway in animals. It is also a key developmental pathway regulating terminal and dorsal-ventral patterning along with many other aspects of embryogenesis. In this review, we focus on the diverse roles for the EGF pathway in Drosophila embryogenesis. We review the existing body of evidence concerning EGF signaling in Drosophila embryogenesis focusing on current uncertainties in the field and areas for future study. This review provides a foundation for utilizing the Drosophila model system for research into EGF effects on cancer...
February 7, 2017: Cancers
https://www.readbyqxmd.com/read/28174264/hippo-signaling-promotes-jnk-dependent-cell-migration
#6
Xianjue Ma, Hongxiang Wang, Jiansong Ji, Wenyan Xu, Yihao Sun, Wenzhe Li, Xiaoping Zhang, Juxiang Chen, Lei Xue
Overwhelming studies show that dysregulation of the Hippo pathway is positively correlated with cell proliferation, growth, and tumorigenesis. Paradoxically, the detailed molecular roles of the Hippo pathway in cell invasion remain debatable. Using a Drosophila invasion model in wing epithelium, we show herein that activated Hippo signaling promotes cell invasion and epithelial-mesenchymal transition through JNK, as inhibition of JNK signaling dramatically blocked Hippo pathway activation-induced matrix metalloproteinase 1 expression and cell invasion...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28166211/divergent-effects-of-intrinsically-active-mek-variants-on-developmental-ras-signaling
#7
Yogesh Goyal, Granton A Jindal, José L Pelliccia, Kei Yamaya, Eyan Yeung, Alan S Futran, Rebecca D Burdine, Trudi Schüpbach, Stanislav Y Shvartsman
Germline mutations in Ras pathway components are associated with a large class of human developmental abnormalities, known as RASopathies, that are characterized by a range of structural and functional phenotypes, including cardiac defects and neurocognitive delays. Although it is generally believed that RASopathies are caused by altered levels of pathway activation, the signaling changes in developing tissues remain largely unknown. We used assays with spatiotemporal resolution in Drosophila melanogaster (fruit fly) and Danio rerio (zebrafish) to quantify signaling changes caused by mutations in MAP2K1 (encoding MEK), a core component of the Ras pathway that is mutated in both RASopathies and cancers in humans...
February 6, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28143872/musashi-rna-binding-proteins-as-cancer-drivers-and-novel-therapeutic-targets
#8
Alexander E Kudinov, John Karanicolas, Erica A Golemis, Yanis Boumber
Aberrant gene expression that drives human cancer can arise from epigenetic dysregulation. While much attention has focused on altered activity of transcription factors and chromatin-modulating proteins, proteins that act post-transcriptionally can potently affect expression of oncogenic signaling proteins. The RNA-binding proteins (RBPs) Musashi-1 (MSI1) and Musashi-2 (MSI2) are emerging as regulators of multiple critical biological processes relevant to cancer initiation, progression, and drug resistance...
January 31, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28126840/neuroblast-niche-position-is-controlled-by-pi3-kinase-dependent-de-cadherin-adhesion
#9
Susan E Doyle, Matthew C Pahl, Karsten H Siller, Lindsay Ardiff, Sarah E Siegrist
Correct positioning of stem cells within their niche is essential for tissue morphogenesis and homeostasis. Yet how stem cells acquire and maintain niche position remains largely unknown. Here, we show that a subset of brain neuroblasts (NBs) in Drosophila utilize PI3-kinase and DE-cadherin to build adhesive contact for NB niche positioning. NBs remain within their native microenvironment when levels of PI3-kinase activity and DE-cadherin are elevated in NBs. This occurs through PI3-kinase dependent regulation of DE-Cadherin mediated cell adhesion between NBs and neighboring cortex glia, and between NBs and their GMC daughters...
January 26, 2017: Development
https://www.readbyqxmd.com/read/28112520/nanothermometry-measure-of-muscle-efficiency
#10
Suvra S Laha, Akshata R Naik, Eric R Kuhn, Maysen Alvarez, Alyson Sujkowski, Robert J Wessells, Bhanu P Jena
Despite recent advances in thermometry, determination of temperature at the nanometer scale in single molecules to live cells remains a challenge that holds great promise in disease detection among others. In the present study, we use a new approach to nanometer scale thermometry with a spatial and thermal resolution of 80 nm and 1 mK respectively, by directly associating 2 nm cadmium telluride quantum dots (CdTe QDs) to the subject under study. The 2 nm CdTe QDs physically adhered to bovine cardiac and rabbit skeletal muscle myosin, enabling the determination of heat released when ATP is hydrolyzed by both myosin motors...
January 24, 2017: Nano Letters
https://www.readbyqxmd.com/read/28108330/pleiotropic-responses-to-methionine-restriction
#11
Gene P Ables, Jay E Johnson
Methionine restriction (MR) extends lifespan across different species. The main responses of rodent models to MR are well-documented in adipose tissue (AT) and liver, which have reduced mass and improved insulin sensitivity, respectively. Recently, molecular mechanisms that improve healthspan have been identified in both organs during MR. In fat, MR induced a futile lipid cycle concomitant with beige AT accumulation, producing elevated energy expenditure. In liver, MR upregulated fibroblast growth factor 21 and improved glucose metabolism in aged mice and in response to a high-fat diet...
January 17, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28089848/sparc-preserves-follicular-epithelium-integrity-in-insect-ovaries
#12
Paula Irles, Saray Ramos, Maria-Dolors Piulachs
The importance of juvenile hormone regulating insect oogenesis suggests looking for genes whose expression is regulated by this hormone. SPARC is a calcium-binding glycoprotein that forms part of the extracellular membranes, which in vertebrates participates in bones mineralization or regulating cell proliferation in some cancer types. This large number of functions described for SPARC in different species might be related to the significant differences in its structure observed when comparing different species-groups...
February 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28087780/oncogenes-without-a-neighboring-tumor-suppressor-gene-are-more-prone-to-amplification
#13
William K K Wu, Xiangchun Li, Xiansong Wang, Rudin Z W Dai, Alfred S L Cheng, Maggie H T Wang, Thomas Kwong, Tai C Chow, Jun Yu, Matthew T V Chan, Sunny H Wong
Focal copy number gains or losses are important genomic hallmarks of cancer. The genomic distribution of oncogenes and tumor-suppressor genes (TSG) in relation to focal copy number aberrations is unclear. Our analysis revealed that the mean distance of TSGs from oncogenes was significantly shorter than that of non-cancer genes, suggesting that oncogenes and TSGs tend to be in close physical proximity in the human genome. Such relationship was conserved in mouse and drosophila. Pan-cancer analysis using data from The Cancer Genome Atlas indicated that oncogenes without a nearby TSG are more prone to amplification...
January 12, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28087714/dlg5-connects-cell-polarity-and-hippo-signaling-protein-networks-by-linking-par-1-with-mst1-2
#14
Julian Kwan, Anna Sczaniecka, Emad Heidary Arash, Liem Nguyen, Chia-Chun Chen, Srdjana Ratkovic, Olga Klezovitch, Liliana Attisano, Helen McNeill, Andrew Emili, Valeri Vasioukhin
Disruption of apical-basal polarity is implicated in developmental disorders and cancer; however, the mechanisms connecting cell polarity proteins with intracellular signaling pathways are largely unknown. We determined previously that membrane-associated guanylate kinase (MAGUK) protein discs large homolog 5 (DLG5) functions in cell polarity and regulates cellular proliferation and differentiation via undefined mechanisms. We report here that DLG5 functions as an evolutionarily conserved scaffold and negative regulator of Hippo signaling, which controls organ size through the modulation of cell proliferation and differentiation...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28079919/copper-oxide-nanoparticles-and-copper-sulphate-act-as-antigenotoxic-agents-in-drosophila-melanogaster
#15
Mohamed Alaraby, Alba Hernández, Ricard Marcos
The biological reactivity of metal and metal oxide nanomaterials is attributed to their redox properties, which would explain their pro- or anti-cancer properties depending on exposure circumstances. In this sense, copper oxide nanoparticles (CuONP) have been proposed as a potential anti-tumoral agent. The aim of this study was to assess if CuONP can exert antigenotoxic effects using Drosophila melanogaster as an in vivo model. Genotoxicity was induced by two well-known genotoxic compounds, namely potassium dichromate (PD) and ethyl methanesulfonate (EMS)...
January 12, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28070290/cancer-brings-forward-oviposition-in-the-fly-drosophila-melanogaster
#16
Audrey Arnal, Camille Jacqueline, Beata Ujvari, Lucas Leger, Céline Moreno, Dominique Faugere, Aurélie Tasiemski, Céline Boidin-Wichlacz, Dorothée Misse, François Renaud, Jacques Montagne, Andreu Casali, Benjamin Roche, Frédéric Mery, Frédéric Thomas
Hosts often accelerate their reproductive effort in response to a parasitic infection, especially when their chances of future reproduction decrease with time from the onset of the infection. Because malignancies usually reduce survival, and hence potentially the fitness, it is expected that hosts with early cancer could have evolved to adjust their life-history traits to maximize their immediate reproductive effort. Despite the potential importance of these plastic responses, little attention has been devoted to explore how cancers influence animal reproduction...
January 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28068320/myc-suppresses-tumor-invasion-and-cell-migration-by-inhibiting-jnk-signaling
#17
X Ma, J Huang, Y Tian, Y Chen, Y Yang, X Zhang, F Zhang, L Xue
Tumor metastasis, but not primary overgrowth, is the leading cause of mortality for cancer patients. During the past decade, Drosophila melanogaster has been well-accepted as an excellent model to address the intrinsic mechanism of different aspects of cancer progression, ranging from tumor initiation to metastasis. In a genetic screen performed in Drosophila, aiming to find novel modulators of tumor invasion, we identified the oncoprotein Myc as a negative regulator. While expression of Myc dramatically blocks tumor invasion and cell migration, loss of Myc promotes cell migration in vivo...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28060321/imaging-of-cell-shape-alteration-and-cell-movement-in-drosophila-gastrulation-using-de-cadherin-reporter-transgenic-flies
#18
M Rezaul Karim, Tomohiro Haruta, Taro Matsumoto, Hiroki Oda, Hiroaki Taniguchi
Gastrulation is the first set of morphologically dynamic events that occur during the embryonic development of multicellular animals such as Drosophila. This morphological alteration is also recognized as epithelial to mesenchymal transition (EMT). Dysregulation of EMT is associated with fibrosis and cancer metastasis. There is emerging evidence that EMT is controlled by a number of molecular mechanisms. As such, many key genes that control apical constriction are also known to be important factors in the EMT observed in cancer metastasis...
December 29, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28057306/the-drosophila-accessory-gland-as-a-model-for-prostate-cancer-and-other-pathologies
#19
C Wilson, A Leiblich, D C I Goberdhan, F Hamdy
The human prostate is a gland of the male reproductive tract, which together with the seminal vesicles, is responsible for most seminal fluid production. It is a common site of cancer, and unlike other glands, it typically enlarges in aging men. In flies, the male accessory glands make many major seminal fluid components. Like their human equivalents, they secrete proteins from several conserved families, including proteases, lectins, and cysteine-rich secretory proteins, some of which interact with sperm and affect fertility...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28057305/stem-cell-based-tumorigenesis-in-adult-drosophila
#20
S X Hou, S R Singh
Recent studies suggest that a small subset of cells within a tumor, the so-called cancer stem cells (CSCs), are responsible for tumor propagation, relapse, and the eventual death of most cancer patients. CSCs may derive from a few tumor-initiating cells, which are either transformed normal stem cells or reprogrammed differentiated cells after acquiring initial cancer-causing mutations. CSCs and normal stem cells share some properties, but CSCs differ from normal stem cells in their tumorigenic ability. Notably, CSCs are usually resistant to chemo- and radiation therapies...
2017: Current Topics in Developmental Biology
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