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https://www.readbyqxmd.com/read/29239688/compromising-asymmetric-stem-cell-division-in-drosophila-central-brain-revisiting-the-connections-with-tumorigenesis
#1
Ana Carmena
Asymmetric cell division (ACD) is an essential process during development for generating cell diversity. In addition, a more recent connection between ACD, cancer and stem cell biology has opened novel and highly intriguing venues in the field. This connection between compromised ACD and tumorigenesis was first demonstrated using Drosophila neural stem cells (neuroblasts, NBs) more than a decade ago and, over the past years, it has also been established in vertebrate stem cells. Here, focusing on Drosophila larval brain NBs, and in light of results recently obtained in our lab, we revisit this connection emphasizing two main aspects: 1) the differences in tumor suppressor activity of different ACD regulators and 2) the potential relevance of environment and temporal window frame for compromised ACD-dependent induction of tumor-like overgrowth...
December 14, 2017: Fly
https://www.readbyqxmd.com/read/29225579/regulation-of-tissue-growth-by-the-mammalian-hippo-signaling-pathway
#2
REVIEW
Kevin I Watt, Kieran F Harvey, Paul Gregorevic
The integrative control of diverse biological processes such as proliferation, differentiation, apoptosis and metabolism is essential to maintain cellular and tissue homeostasis. Disruption of these underlie the development of many disease states including cancer and diabetes, as well as many of the complications that arise as a consequence of aging. These biological outputs are governed by many cellular signaling networks that function independently, and in concert, to convert changes in hormonal, mechanical and metabolic stimuli into alterations in gene expression...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29218879/an-ultra-fast-and-scalable-quantification-pipeline-for-transposable-elements-from-next-generation-sequencing-data
#3
Hyun-Hwan Jeong, Hari Krishna Yalamanchili, Caiwei Guo, Joshua M Shulman, Zhandong Liu
Transposable elements (TEs) are DNA sequences which are capable of moving from one location to another and represent a large proportion (45%) of the human genome. TEs have functional roles in a variety of biological phenomena such as cancer, neurodegenerative disease, and aging. Rapid development in RNA-sequencing technology has enabled us, for the first time, to study the activity of TE at the systems level.However, efficient TE analysis tools are not yet developed. In this work, we developed SalmonTE, a fast and reliable pipeline for the quantification of TEs from RNA-seq data...
2018: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/29213118/vitamin-k2-prevents-lymphoma-in-drosophila
#4
Maytham A Dragh, Zhiliang Xu, Zainab S Al-Allak, Ling Hong
Previous studies have established the anticancer effect of vitamin K2 (VK2). However, its effect on lymphoma induced by UBIAD1/heix mutation in Drosophila remains unknown. Therefore, we aimed to develop an in vivo model of lymphoma for the precise characterization of lymphoma phenotypes. We also aimed to improve the understanding of the mechanisms that underlie the preventative effects of VK2 on lymphoma. Our results demonstrated that VK2 prevents lymphoma by acting as an electron carrier and by correcting the function and structure of mitochondria by inhibiting mitochondrial reactive oxygen species production mtROS...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29208636/homeodomain-interacting-protein-kinase-promotes-tumorigenesis-and-metastatic-cell-behavior
#5
Jessica A Blaquiere, Kenneth Kin Lam Wong, Stephen D Kinsey, Jin Wu, Esther M Verheyen
Aberrations in signaling pathways that regulate tissue growth often lead to tumorigenesis. Homeodomain interacting protein kinase (Hipk) family members are reported to have distinct and contradictory effects on cell proliferation and tissue growth. From these studies it is clear that much remains to be learned about the roles of Hipk family protein kinases in proliferation and cell behaviour. Previous work has shown that Drosophila Hipk is a potent growth regulator, thus we predicted that it could have a role in tumorigenesis...
November 20, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29203701/regulation-of-carbohydrate-energy-metabolism-in-drosophila-melanogaster
#6
Jaakko Mattila, Ville Hietakangas
Carbohydrate metabolism is essential for cellular energy balance as well as for the biosynthesis of new cellular building blocks. As animal nutrient intake displays temporal fluctuations and each cell type within the animal possesses specific metabolic needs, elaborate regulatory systems are needed to coordinate carbohydrate metabolism in time and space. Carbohydrate metabolism is regulated locally through gene regulatory networks and signaling pathways, which receive inputs from nutrient sensors as well as other pathways, such as developmental signals...
December 2017: Genetics
https://www.readbyqxmd.com/read/29202761/hilbert-schmidt-and-sobol-sensitivity-indices-for-static-and-time-series-wnt-signaling-measurements-in-colorectal-cancer-part-a
#7
Shriprakash Sinha
BACKGROUND: Ever since the accidental discovery of Wingless [Sharma R.P., Drosophila information service, 1973, 50, p 134], research in the field of Wnt signaling pathway has taken significant strides in wet lab experiments and various cancer clinical trials, augmented by recent developments in advanced computational modeling of the pathway. Information rich gene expression profiles reveal various aspects of the signaling pathway and help in studying different issues simultaneously. Hitherto, not many computational studies exist which incorporate the simultaneous study of these issues...
December 4, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/29199019/widespread-rewiring-of-genetic-networks-upon-cancer-signaling-pathway-activation
#8
Maximilian Billmann, Varun Chaudhary, Mostafa F ElMaghraby, Bernd Fischer, Michael Boutros
Cellular signaling networks coordinate physiological processes in all multicellular organisms. Within networks, modules switch their function to control signaling activity in response to the cellular context. However, systematic approaches to map the interplay of such modules have been lacking. Here, we generated a context-dependent genetic interaction network of a metazoan's signaling pathway. Using Wnt signaling in Drosophila as a model, we measured >290,000 double perturbations of the pathway in a baseline state, after activation by Wnt ligand or after loss of the tumor suppressor APC...
November 27, 2017: Cell Systems
https://www.readbyqxmd.com/read/29193257/fundamental-structural-and-functional-properties-of-aquaporin-ion-channels-found-across-the-kingdoms-of-life
#9
Mohamad Kourghi, Jinxin V Pei, Michael L De Ieso, Saeed Nourmohammadi, Pak Hin Chow, Andrea J Yool
Aquaporin (AQP) channels in the Major Intrinsic Protein (MIP) family are known to facilitate transmembrane water fluxes in prokaryotes and eukaryotes. Some classes of AQPs also conduct ions, glycerol, urea, CO2 , nitric oxide, and other small solutes. Ion channel activity has been demonstrated for mammalian AQPs 0, 1, 6, Drosophila big brain (BIB), soybean nodulin 26, and rockcress AtPIP2;1. More classes are likely to be discovered. Newly identified blockers are providing essential tools for establishing physiological roles of some of the AQP dual water and ion channels...
November 29, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29189094/fijiwingspolarity-an-open-source-toolkit-for-semi-automated-detection-of-cell-polarity
#10
Leonard L Dobens, Anna Shipman, Jeffrey D Axelrod
Epithelial cells are defined by apical-basal and planar cell polarity (PCP) signaling, the latter of which establishes an orthogonal plane of polarity in the epithelial sheet. PCP signaling is required for normal cell migration, differentiation, stem cell generation and tissue repair, and defects in PCP have been associated with developmental abnormalities, neuropathologies and cancers. While the molecular mechanism of PCP is incompletely understood, the deepest insights have come from Drosophila, where PCP is manifest in hairs and bristles across the adult cuticle and organization of the ommatidia in the eye...
November 30, 2017: Fly
https://www.readbyqxmd.com/read/29149408/function-of-translationally-controlled-tumor-protein-in-organ-growth-lessons-from-drosophila-studies
#11
Kwang-Wook Choi, Sung-Tae Hong, Thao Phuong Le
Regulation of cell growth and proliferation is crucial for development and function of organs in all animals. Genetic defects in growth control can lead to developmental disorders and cancers. Translationally controlled tumor protein (TCTP) is a family of evolutionarily conserved proteins implicated in cancer. Recent studies have revealed multiple roles of TCTP in diverse cellular events, but TCTP functions in vivo are poorly understood in vertebrate systems. We have used Drosophila melanogaster, the fruit fly, as a model organism for genetic dissection of Tctp function...
2017: Results and Problems in Cell Differentiation
https://www.readbyqxmd.com/read/29141951/selector-genes-display-tumor-cooperation-and-inhibition-in-drosophila-epithelium-in-a-developmental-context-dependent-manner
#12
Ram Prakash Gupta, Anjali Bajpai, Pradip Sinha
During animal development, selector genes determine identities of body segments and those of individual organs. Selector genes are also misexpressed in cancers, although their contributions to tumor progression per se remain poorly understood. Using a model of cooperative tumorigenesis, we show that gain of selector genes results in tumor cooperation, but in only select developmental domains of the wing, haltere and eye-antennal imaginal discs of Drosophila larva. Thus, the field selector, Eyeless (Ey), and the segment selector, Ultrabithorax (Ubx), readily cooperate to bring about neoplastic transformation of cells displaying somatic loss of the tumor suppressor, Lgl, but in only those developmental domains that express the homeo-box protein, Homothorax (Hth), and/or the Zinc-finger protein, Teashirt (Tsh)...
November 15, 2017: Biology Open
https://www.readbyqxmd.com/read/29135915/evaluation-of-polyamine-transport-inhibitors-in-a-drosophila-epithelial-model-suggests-the-existence-of-multiple-transport-systems
#13
Minpei Wang, Otto Phanstiel, Laurence von Kalm
Increased polyamine biosynthesis activity and an active polyamine transport system are characteristics of many cancer cell lines and polyamine depletion has been shown to be a viable anticancer strategy. Polyamine levels can be depleted by difluoromethylornithine (DFMO), an inhibitor of the key polyamine biosynthesis enzyme ornithine decarboxylase (ODC). However, malignant cells frequently circumvent DFMO therapy by up-regulating polyamine import. Therefore, there is a need to develop compounds that inhibit polyamine transport...
November 14, 2017: Medical Sciences: Open Access Journal
https://www.readbyqxmd.com/read/29130960/piwi-proteins-and-piwi-interacting-rna-emerging-roles-in-cancer
#14
Yi-Neng Han, Yuan Li, Sheng-Qiang Xia, Yuan-Yuan Zhang, Jun-Hua Zheng, Wei Li
P-Element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a type of noncoding RNAs (ncRNAs) and interact with PIWI proteins. piRNAs were primarily described in the germline, but emerging evidence revealed that piRNAs are expressed in a tissue-specific manner among multiple human somatic tissue types as well and play important roles in transposon silencing, epigenetic regulation, gene and protein regulation, genome rearrangement, spermatogenesis and germ stem-cell maintenance. PIWI proteins were first discovered in Drosophila and they play roles in spermatogenesis, germline stem-cell maintenance, self-renewal, retrotransposons silencing and the male germline mobility control...
November 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29127201/loss-of-the-mucosal-barrier-alters-the-progenitor-cell-niche-via-jak-stat-signaling
#15
Liping Zhang, Katharina Ribbeck, Bradley Turner, Kelly G Ten Hagen
The mucous barrier of our digestive tract is the first line of defense against pathogens and damage. Disruptions in this barrier are associated with diseases such as Crohn's disease, colitis and colon cancer, but mechanistic insights into these processes and diseases are limited. We have previously shown that loss of a conserved O-glycosyltransferase (PGANT4) in Drosophila results in aberrant secretion of components of the peritrophic/mucous membrane in the larval digestive tract. Here, we show that loss of pgant4 disrupts the mucosal barrier, resulting in epithelial expression of the IL-6-like cytokine Upd3, leading to activation of JAK/STAT signaling, differentiation of cells that form the progenitor cell niche and abnormal proliferation of progenitor cells...
November 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29093681/quantitative-and-systems-pharmacology-3-network-based-identification-of-new-targets-for-natural-products-enables-potential-uses-in-aging-associated-disorders
#16
Jiansong Fang, Li Gao, Huili Ma, Qihui Wu, Tian Wu, Jun Wu, Qi Wang, Feixiong Cheng
Aging that refers the accumulation of genetic and physiology changes in cells and tissues over a lifetime has been shown a high risk of developing various complex diseases, such as neurodegenerative disease, cardiovascular disease and cancer. Over the past several decades, natural products have been demonstrated as anti-aging interveners via extending lifespan and preventing aging-associated disorders. In this study, we developed an integrated systems pharmacology infrastructure to uncover new indications for aging-associated disorders by natural products...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29069438/loss-of-heparan-sulfate-in-the-niche-leads-to-tumor-like-germ-cell-growth-in-the-drosophila-testis
#17
Daniel C Levings, Hiroshi Nakato
The stem cell niche normally prevents aberrant stem cell behaviors that lead to cancer formation. Recent studies suggest that some cancers are derived from endogenous populations of adult stem cells that have somehow escaped from normal control by the niche. However, the molecular mechanisms by which the niche retains stem cells locally and tightly controls their divisions are poorly understood. Here, we demonstrate that the presence of heparan sulfate (HS), a class glygosaminoglycan chains, in the Drosophila germline stem cell niche prevents tumor formation in the testis...
October 23, 2017: Glycobiology
https://www.readbyqxmd.com/read/29065309/pwp1-mediates-nutrient-dependent-growth-control-through-nucleolar-regulation-of-ribosomal-gene-expression
#18
Ying Liu, Jaakko Mattila, Sami Ventelä, Leena Yadav, Wei Zhang, Nicole Lamichane, Jari Sundström, Otto Kauko, Reidar Grénman, Markku Varjosalo, Jukka Westermarck, Ville Hietakangas
Ribosome biogenesis regulates animal growth and is controlled by nutrient-responsive mTOR signaling. How ribosome biogenesis is regulated during the developmental growth of animals and how nutrient-responsive signaling adjusts ribosome biogenesis in this setting have remained insufficiently understood. We uncover PWP1 as a chromatin-associated regulator of developmental growth with a conserved role in RNA polymerase I (Pol I)-mediated rRNA transcription. We further observed that PWP1 epigenetically maintains the rDNA loci in a transcription-competent state...
October 23, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29049360/the-bacterial-virulence-factor-caga-induces-microbial-dysbiosis-that-contributes-to-excessive-epithelial-cell-proliferation-in-the-drosophila-gut
#19
Tiffani Alvey Jones, Diane Z Hernandez, Zoë C Wong, Anica M Wandler, Karen Guillemin
Gut microbiota facilitate many aspects of human health and development, but dysbiotic microbiota can promote hyperplasia and inflammation and contribute to human diseases such as cancer. Human patients infected with the gastric cancer-causing bacterium Helicobacter pylori have altered microbiota; however, whether dysbiosis contributes to disease in this case is unknown. Many H. pylori human disease phenotypes are associated with a potent virulence protein, CagA, which is translocated into host epithelial cells where it alters cell polarity and manipulates host-signaling pathways to promote disease...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29035383/extracellular-nme-proteins-a-player-or-a-bystander
#20
Patrizia Romani, Marilena Ignesti, Giuseppe Gargiulo, Tien Hsu, Valeria Cavaliere
The Nm23/NME gene family has been under intensive study since Nm23H1/NME1 was identified as the first metastasis suppressor. Inverse correlation between the expression levels of NME1/2 and prognosis has indeed been demonstrated in different tumor cohorts. Interestingly, the presence of NME proteins in the extracellular environment in normal and tumoral conditions has also been noted. In many reported cases, however, these extracellular NME proteins exhibit anti-differentiation or oncogenic functions, contradicting their canonical anti-metastatic action...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
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