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https://www.readbyqxmd.com/read/28422722/the-clinical-value-regulatory-mechanisms-and-gene-network-of-the-cancer-testis-gene-stk31-in-pancreatic-cancer
#1
Kai Zhang, Zipeng Lu, Yi Zhu, Lei Tian, Jingjing Zhang, Chunhua Xi, Wentao Gao, Kuirong Jiang, Yi Miao
We aimed to identify STK31 as a cancer-testis (CT) gene and to explore its potential clinical value, regulatory mechanisms, and gene network in pancreatic cancer (PC). Gene expression data were generated from normal organ samples and pancreatic cancer samples from three public databases. STK31 expression patterns in normal and PC tissues were identified, and we explored its regulatory mechanisms. Gene ontology (GO) and pathway analyses of STK31-related genes were performed and an STK31 protein-protein interaction (PPI) network was constructed...
April 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28420161/myc-cell-competition-and-cell-death-in-cancer-the-inseparable-triad
#2
REVIEW
Simone Di Giacomo, Manuela Sollazzo, Simona Paglia, Daniela Grifoni
Deregulation of MYC family proteins in cancer is associated with a global reprogramming of gene expression, ultimately promoting glycolytic pathways, cell growth, and proliferation. It is well known that MYC upregulation triggers cell-autonomous apoptosis in normal tissues, while frankly malignant cells develop resistance to apoptotic stimuli, partly resulting from MYC addiction. As well as inducing cell-autonomous apoptosis, MYC upregulation is able to trigger non cell-autonomous apoptotic death through an evolutionarily conserved mechanism known as "cell competition"...
April 17, 2017: Genes
https://www.readbyqxmd.com/read/28404605/proteomics-analysis-identifies-orthologs-of-human-chitinase-like-proteins-as-inducers-of-tube-morphogenesis-defects-in-drosophila
#3
Sandra G Zimmerman, Gennifer E Merrihew, Michael J MacCoss, Celeste A Berg
Elevated levels of human chitinase-like proteins (CLPs) are associated with numerous chronic inflammatory diseases and several cancers, often correlating with poor prognosis. Nevertheless, there is scant knowledge of their function. The CLPs normally mediate immune responses and wound healing, and when upregulated, they can promote disease progression by remodeling tissue, activating signaling cascades, stimulating proliferation and migration, and by regulating adhesion. We identified Imaginal disc growth factors (Idgfs), orthologs of human CLPs CHI3L1, CHI3L2, and OVGP1, in a proteomics analysis designed to discover factors that regulate tube morphogenesis in a Drosophila melanogaster model of tube formation...
April 12, 2017: Genetics
https://www.readbyqxmd.com/read/28401354/novel-triazole-linked-2-phenyl-benzoxazole-derivatives-induce-apoptosis-by-inhibiting-mir-2-mir-13-and-mir-14-function-in-drosophila-melanogaster
#4
Tanmoy Mondal, A V S Lavanya, Akash Mallick, Tulshiram L Dadmala, Ravindra M Kumbhare, Utpal Bhadra, Manika Pal Bhadra
Apoptosis is an important phenomenon in multi cellular organisms for maintaining tissue homeostasis and embryonic development. Defect in apoptosis leads to a number of disorders like- autoimmune disorder, immunodeficiency and cancer. 21-22 nucleotides containing micro RNAs (miRNAs/miRs) function as a crucial regulator of apoptosis alike other cellular pathways. Recently, small molecules have been identified as a potent inducer of apoptosis. In this study, we have identified novel Triazole linked 2-phenyl benzoxazole derivatives (13j and 13h) as a negative regulator of apoptosis inhibiting micro RNAs (miR-2, miR-13 and miR-14) in a well established in vivo model Drosophila melanogaster where the process of apoptosis is very similar to human apoptosis...
June 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28398229/controlling-the-master-chromatin-dynamics-at-the-myc-promoter-integrate-developmental-signaling
#5
REVIEW
Olga Zaytseva, Leonie M Quinn
The transcription factor and cell growth regulator MYC is potently oncogenic and estimated to contribute to most cancers. Decades of attempts to therapeutically target MYC directly have not resulted in feasible clinical applications, and efforts have moved toward indirectly targeting MYC expression, function and/or activity to treat MYC-driven cancer. A multitude of developmental and growth signaling pathways converge on the MYC promoter to modulate transcription through their downstream effectors. Critically, even small increases in MYC abundance (<2 fold) are sufficient to drive overproliferation; however, the details of how oncogenic/growth signaling networks regulate MYC at the level of transcription remain nebulous even during normal development...
April 11, 2017: Genes
https://www.readbyqxmd.com/read/28396508/adipocyte-metabolic-pathways-regulated-by-diet-control-the-female-germline-stem-cell-lineage-in-drosophila
#6
Shinya Matsuoka, Alissa Armstrong, Leesa L Sampson, Kaitlin M Laws, Daniela Drummond-Barbosa
Nutrients affect adult stem cells through complex mechanisms involving multiple organs. Adipocytes are highly sensitive to diet and have key metabolic roles, and obesity increases the risk for many cancers. How diet-regulated adipocyte metabolic pathways influence normal stem cell lineages, however, remains unclear. Drosophila melanogaster has highly conserved adipocyte metabolism and a well-characterized female germline stem cell (GSC) lineage response to diet. Here, we conducted an isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to identify diet-regulated adipocyte metabolic pathways that control the female GSC lineage...
April 10, 2017: Genetics
https://www.readbyqxmd.com/read/28389882/hormetic-efficacy-of-rutin-to-promote-longevity-in-drosophila-melanogaster
#7
Debarati Chattopadhyay, Atith Chitnis, Aishwarya Talekar, Prajakta Mulay, Manyata Makkar, Joel James, Kavitha Thirumurugan
Hormetins are compounds that mediate hormesis by being beneficial at low doses but detrimental at high doses. Recent studies have highlighted that many compounds that extended lifespan in model organisms did so by mediating hormesis. Rutin is a glycosylate conjugate of quercetin and rutinose and is abundant in citrus fruits and buckwheat seeds. Rutin possess ROS scavenging, anti-cancer, cardio-protective, skin-regenerative and neuro-protective properties. Drosophila melanogaster is an attractive model organism for longevity studies owing to its homology of organ and cellular-pathways with mammals...
April 7, 2017: Biogerontology
https://www.readbyqxmd.com/read/28382676/natural-genomic-amplification-of-cholinesterase-genes-in-animals
#8
REVIEW
Arnaud Chatonnet, Nicolas Lenfant, Pascale Marchot, Murray E Selkirk
Tight control of the concentration of acetylcholine at cholinergic synapses requires precise regulation of the number and state of the acetylcholine receptors, and of the synthesis and degradation of the neurotransmitter. In particular, the cholinesterase activity has to be controlled exquisitely. In the genome of the first experimental models used (man, mouse, zebrafish and drosophila), there are only one or two genes coding for cholinesterases, whereas there are more genes for their closest relatives the carboxylesterases...
April 5, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28374738/quantitative-3d-analysis-of-complex-single-border-cell-behaviors-in-coordinated-collective-cell-migration
#9
Adam Cliffe, David P Doupé, HsinHo Sung, Isaac Kok Hwee Lim, Kok Haur Ong, Li Cheng, Weimiao Yu
Understanding the mechanisms of collective cell migration is crucial for cancer metastasis, wound healing and many developmental processes. Imaging a migrating cluster in vivo is feasible, but the quantification of individual cell behaviours remains challenging. We have developed an image analysis toolkit, CCMToolKit, to quantify the Drosophila border cell system. In addition to chaotic motion, previous studies reported that the migrating cells are able to migrate in a highly coordinated pattern. We quantify the rotating and running migration modes in 3D while also observing a range of intermediate behaviours...
April 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28363972/myosin-ii-promotes-the-anisotropic-loss-of-the-apical-domain-during-drosophila-neuroblast-ingression
#10
Sérgio Simões, Youjin Oh, Michael F Z Wang, Rodrigo Fernandez-Gonzalez, Ulrich Tepass
Epithelial-mesenchymal transitions play key roles in development and cancer and entail the loss of epithelial polarity and cell adhesion. In this study, we use quantitative live imaging of ingressing neuroblasts (NBs) in Drosophila melanogaster embryos to assess apical domain loss and junctional disassembly. Ingression is independent of the Snail family of transcriptional repressors and down-regulation of Drosophila E-cadherin (DEcad) transcription. Instead, the posttranscriptionally regulated decrease in DEcad coincides with the reduction of cell contact length and depends on tension anisotropy between NBs and their neighbors...
March 31, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28350987/the-super-elongation-complex-drives-neural-stem-cell-fate-commitment
#11
Kun Liu, Dan Shen, Jingwen Shen, Shihong M Gao, Bo Li, Chouin Wong, Weidong Feng, Yan Song
Asymmetric stem cell division establishes an initial difference between a stem cell and its differentiating sibling, critical for maintaining homeostasis and preventing carcinogenesis. Yet the mechanisms that consolidate and lock in such initial fate bias remain obscure. Here, we use Drosophila neuroblasts to demonstrate that the super elongation complex (SEC) acts as an intrinsic amplifier to drive cell fate commitment. SEC is highly expressed in neuroblasts, where it promotes self-renewal by physically associating with Notch transcription activation complex and enhancing HES (hairy and E(spl)) transcription...
March 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28343031/assessing-the-genotoxic-effects-of-two-lipid-peroxidation-products-4-oxo-2-nonenal-and-4-hydroxy-hexenal-in-haemocytes-and-midgut-cells-of-drosophila-melanogaster-larvae
#12
Eşref Demir, Ricard Marcos
Lipid peroxidation products can induce tissue damage and are implicated in diverse pathological conditions, including aging, atherosclerosis, brain disorders, cancer, lung and various liver disorders. Since in vivo studies produce relevant information, we have selected Drosophila melanogaster as a suitable in vivo model to characterise the potential risks associated to two lipid peroxidation products namely 4-oxo-2-nonenal (4-ONE) and 4-hydroxy-hexenal (4-HHE). Toxicity, intracellular reactive oxygen species production, and genotoxicity were the end-points evaluated...
March 22, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28340370/validation-of-comet-assay-in-oregon-r-and-wild-type-strains-of-drosophila-melanogaster-exposed-to-a-natural-radioactive-environment-in-brazilian-semiarid-region
#13
Cícero Jorge Verçosa, Aroldo Vieira de Moraes Filho, Ícaro Fillipe de Araújo Castro, Robson Gomes Dos Santos, Kenya Silva Cunha, Daniela de Melo E Silva, Ana Cristina Lauer Garcia, Julio Alejandro Navoni, Viviane Souza do Amaral, Claudia Rohde
Natural radiation of geological origin is a common phenomenon in Brazil, a country where radioactive agents such as uranium may be often found. As an unstable atom, uranium undergoes radioactive decay with the generation of a series of decay by-products, including radon, which may be highly genotoxic and trigger several pathological processes, among which cancer. Because it is a gas, radon may move freely between cracks and gaps in the ground, seeping upwards into the buildings and in the environment. In this study, two Drosophila melanogaster Meigen (Diptera, Drosophilidae) strains called Oregon-R and Wild (collected in a non-radioactive environment) were exposed to atmospheric radiation in the Lajes Pintadas city, in the semiarid zone of northeastern Brazil...
March 21, 2017: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/28304334/kdm2-family-members-are-regulated-by-hif-1-in-hypoxia
#14
Michael Batie, Jimena Druker, Laura D'Ignazio, Sonia Rocha
Hypoxia is not only a developmental cue but also a stress and pathological stimulus in many human diseases. The response to hypoxia at the cellular level relies on the activity of the transcription factor family, hypoxia inducible factor (HIF). HIF-1 is responsible for the acute response and transactivates a variety of genes involved in cellular metabolism, cell death, and cell growth. Here, we show that hypoxia results in increased mRNA levels for human lysine (K)-specific demethylase 2 (KDM2) family members, KDM2A and KDM2B, and also for Drosophila melanogaster KDM2, a histone and protein demethylase...
March 17, 2017: Cells
https://www.readbyqxmd.com/read/28301874/veph1-expression-decreases-vascularisation-in-ovarian-cancer-xenografts-and-inhibits-vegfa-and-il8-expression-through-inhibition-of-akt-activation
#15
Premalatha Shathasivam, Alexandra Kollara, Thomasina Spybey, Soyeon Park, Blaise Clarke, Maurice J Ringuette, Theodore J Brown
BACKGROUND: VEPH1 is amplified in several cancers including ovarian but its impact on tumour progression is unknown. Previous work has shown that VEPH1 inhibits TGFβ signalling while its Drosophila ortholog increases tissue growth, raising the possibility that VEPH1 could impact tumour growth or progression. METHODS: A CRISPR approach was used to disrupt VEPH1 expression in ovarian cancer ES-2 cells, while VEPH1-negative SKOV3 cells were stably transfected with VEPH1 cDNA...
April 11, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28281543/egfr-arf6-regulation-of-hh-signalling-stimulates-oncogenic-ras-tumour-overgrowth
#16
Chiswili Chabu, Da-Ming Li, Tian Xu
Multiple signalling events interact in cancer cells. Oncogenic Ras cooperates with Egfr, which cannot be explained by the canonical signalling paradigm. In turn, Egfr cooperates with Hedgehog signalling. How oncogenic Ras elicits and integrates Egfr and Hedgehog signals to drive overgrowth remains unclear. Using a Drosophila tumour model, we show that Egfr cooperates with oncogenic Ras via Arf6, which functions as a novel regulator of Hh signalling. Oncogenic Ras induces the expression of Egfr ligands. Egfr then signals through Arf6, which regulates Hh transport to promote Hh signalling...
March 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28278156/a-new-mode-of-dna-binding-distinguishes-capicua-from-other-hmg-box-factors-and-explains-its-mutation-patterns-in-cancer
#17
Marta Forés, Lucía Simón-Carrasco, Leiore Ajuria, Núria Samper, Sergio González-Crespo, Matthias Drosten, Mariano Barbacid, Gerardo Jiménez
HMG-box proteins, including Sox/SRY (Sox) and TCF/LEF1 (TCF) family members, bind DNA via their HMG-box. This binding, however, is relatively weak and both Sox and TCF factors employ distinct mechanisms for enhancing their affinity and specificity for DNA. Here we report that Capicua (CIC), an HMG-box transcriptional repressor involved in Ras/MAPK signaling and cancer progression, employs an additional distinct mode of DNA binding that enables selective recognition of its targets. We find that, contrary to previous assumptions, the HMG-box of CIC does not bind DNA alone but instead requires a distant motif (referred to as C1) present at the C-terminus of all CIC proteins...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28275687/hedgehog-signaling-links-chronic-inflammation-to-gastric-cancer-precursor-lesions
#18
REVIEW
Juanita L Merchant, Lin Ding
Since its initial discovery in Drosophila, Hedgehog (HH) signaling has long been associated with foregut development. The mammalian genome expresses 3 HH ligands, with sonic hedgehog (SHH) levels highest in the mucosa of the embryonic foregut. More recently, interest in the pathway has shifted to improving our understanding of its role in gastrointestinal cancers. The use of reporter mice proved instrumental in our ability to probe the expression pattern of SHH ligand and the cell types responding to canonical HH signaling during homeostasis, inflammation, and neoplastic transformation...
March 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28272458/modulation-of-lat1-slc7a5-transporter-activity-and-stability-by-membrane-cholesterol
#19
David Dickens, George N Chiduza, Gareth S A Wright, Munir Pirmohamed, Svetlana V Antonyuk, S Samar Hasnain
LAT1 (SLC7A5) is a transporter for both the uptake of large neutral amino acids and a number of pharmaceutical drugs. It is expressed in numerous cell types including T-cells, cancer cells and brain endothelial cells. However, mechanistic knowledge of how it functions and its interactions with lipids are unknown or limited due to inability of obtaining stable purified protein in sufficient quantities. Our data show that depleting cellular cholesterol reduced the Vmax but not the Km of the LAT1 mediated uptake of a model substrate into cells (L-DOPA)...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28271570/single-domain-antibodies-for-the-knockdown-of-cytosolic-and-nuclear-proteins
#20
REVIEW
Thomas Böldicke
Single domain antibodies (sdAbs) from camels or sharks comprise only the variable heavy chain domain. Human sdAbs comprise the variable domain of the heavy chain (VH) or light chain (VL) and can be selected from human antibodies. SdAbs are stable, non aggregating molecules in vitro and in vivo compared to complete antibodies and scFv fragments. They are excellent novel inhibitors of cytosolic/nuclear proteins because they are correctly folded inside the cytosol in contrast to scFv fragments. SdAbs are unique because of their excellent specificity and possibility to target posttranslational modifications such as phosphorylation sites, conformers or interaction regions of proteins that cannot be targeted with genetic knockout techniques and are impossible to knockdown with RNAi...
March 8, 2017: Protein Science: a Publication of the Protein Society
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