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https://www.readbyqxmd.com/read/28916802/local-juvenile-hormone-activity-regulates-gut-homeostasis-and-tumor-growth-in-adult-drosophila
#1
M M Rahman, X Franch-Marro, J L Maestro, D Martin, A Casali
Hormones play essential roles during development and maintaining homeostasis in adult organisms, regulating a plethora of biological processes. Generally, hormones are secreted by glands and perform a systemic action. Here we show that Juvenile Hormones (JHs), insect sesquiterpenoids synthesized by the corpora allata, are also synthesized by the adult Drosophila gut. This local, gut specific JH activity, is synthesized by and acts on the intestinal stem cell and enteroblast populations, regulating their survival and cellular growth through the JH receptors Gce/Met and the coactivator Tai...
September 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912546/phosphoenolpyruvate-carboxykinase-maintains-glycolysis-driven-growth-in-drosophila-tumors
#2
Rashid Hussain, Zeeshan Shaukat, Mahwish Khan, Robert Saint, Stephen L Gregory
Tumors frequently fail to pass on all their chromosomes correctly during cell division, and this chromosomal instability (CIN) causes irregular aneuploidy and oxidative stress in cancer cells. Our objective was to test knockdowns of metabolic enzymes in Drosophila to find interventions that could exploit the differences between normal and CIN cells to block CIN tumor growth without harming the host animal. We found that depleting by RNAi or feeding the host inhibitors against phosphoenolpyruvate carboxykinase (PEPCK) was able to block the growth of CIN tissue in a brat tumor explant model...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28870988/a-fluorescent-toolkit-for-spatiotemporal-tracking-of-apoptotic-cells-in-living-drosophila-tissues
#3
Sonia Schott, Arnaud Ambrosini, Audrey Barbaste, Corinne Benassayag, Mélanie Gracia, Amsha Proag, Mégane Rayer, Bruno Monier, Magali Suzanne
Far from being passive, apoptotic cells influence their environment. For instance, they promote tissue folding, myoblast fusion and modulate tumor growth. Understanding the role of apoptotic cells necessitates their efficient tracking within living tissues, a task which is currently challenging. In order to easily spot apoptotic cells in developing Drosophila tissues, we generated a series of fly lines expressing different fluorescent sensors of caspase activity. We show that three of these reporters (GFP, Cerulean and Venus derived molecules) are detected specifically in apoptotic cells and throughout the whole process of programmed cell death...
September 4, 2017: Development
https://www.readbyqxmd.com/read/28859078/the-wagr-syndrome-gene-prrg4-is-a-functional-homologue-of-the-commissureless-axon-guidance-gene
#4
Elizabeth D Justice, Sarah J Barnum, Thomas Kidd
WAGR syndrome is characterized by Wilm's tumor, aniridia, genitourinary abnormalities and intellectual disabilities. WAGR is caused by a chromosomal deletion that includes the PAX6, WT1 and PRRG4 genes. PRRG4 is proposed to contribute to the autistic symptoms of WAGR syndrome, but the molecular function of PRRG4 genes remains unknown. The Drosophila commissureless (comm) gene encodes a short transmembrane protein characterized by PY motifs, features that are shared by the PRRG4 protein. Comm intercepts the Robo axon guidance receptor in the ER/Golgi and targets Robo for degradation, allowing commissural axons to cross the CNS midline...
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28853394/tumor-promoting-function-of-apoptotic-caspases-by-an-amplification-loop-involving-ros-macrophages-and-jnk-in-drosophila
#5
Andreas Bergmann, Ernesto Perez, Jillian L Lindblad
Apoptosis and its molecular mediators, the caspases, have long been regarded as tumor suppressors and one hallmark of cancer is "Evading Apoptosis". However, recent work has suggested that apoptotic caspases can also promote proliferation and tumor growth under certain conditions. How caspases promote proliferation and how cells are protected from the potentially harmful action of apoptotic caspases is largely unknown. Here, we show that although caspases are activated in a well-studied neoplastic tumor model in Drosophila, oncogenic mutations of the proto-oncogene Ras (Ras(V12)) maintain tumorous cells in an "undead"-like condition and transform caspases from tumor suppressors into tumor promotors...
August 30, 2017: ELife
https://www.readbyqxmd.com/read/28846972/mutagenic-recombinogenic-and-carcinogenic-potential-of-thiamethoxam-insecticide-and-formulated-product-in-somatic-cells-of%C3%A2-drosophila-melanogaster
#6
Cássio Resende de Morais, Stephan Malfitano Carvalho, Maria Paula Carvalho Naves, Galber Araujo, Alexandre Azenha Alves de Rezende, Ana Maria Bonetti, Mário Antônio Spanó
Thiamethoxam (TMX) belongs to a class of neuro-active insecticides referred as neonicotinoids, while actara(®) (AC) is one of the most popular TMX-based products in Brazil. The aim of this study was to evaluate the mutagenic, recombinogenic and carcinogenic potential of TMX and AC insecticides. The mutagenic and recombinogenic effect of TMX and AC were evaluated in vivo by the Somatic Mutation and Recombination Test (SMART) while carcinogenic effects were evaluated through the Test for Detection of Epithelial Tumor Clones (wts test), both in somatic cells of Drosophila melanogaster...
August 19, 2017: Chemosphere
https://www.readbyqxmd.com/read/28834743/constitutive-immune-activity-promotes-tumorigenesis-in-drosophila-intestinal-progenitor%C3%A2-cells
#7
Kristina Petkau, Meghan Ferguson, Silvia Guntermann, Edan Foley
Gut innate immune defenses control bacterial populations and protect the host interior from invasion. Although excess intestinal immune activity frequently promotes inflammatory illnesses, we know little about the consequences of chronic innate immune activity exclusively in endodermal gut cells of an otherwise normal animal. To address this question, we examined the consequences of persistent inflammatory signals in adult fly intestinal progenitor cells. We found that constitutive immune activity disrupts expression of homeostatic regulators such as Notch pathway components and induces hyperplasia throughout the gut...
August 22, 2017: Cell Reports
https://www.readbyqxmd.com/read/28827401/inactivation-of-capicua-in-adult-mice-causes-t-cell-lymphoblastic-lymphoma
#8
Lucía Simón-Carrasco, Osvaldo Graña, Marina Salmón, Harrys K C Jacob, Alejandro Gutierrez, Gerardo Jiménez, Matthias Drosten, Mariano Barbacid
CIC (also known as Capicua) is a transcriptional repressor negatively regulated by RAS/MAPK signaling. Whereas the functions of Cic have been well characterized in Drosophila, little is known about its role in mammals. CIC is inactivated in a variety of human tumors and has been implicated recently in the promotion of lung metastases. Here, we describe a mouse model in which we inactivated Cic by selectively disabling its DNA-binding activity, a mutation that causes derepression of its target genes. Germline Cic inactivation causes perinatal lethality due to lung differentiation defects...
July 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28808034/feedback-amplification-loop-drives-malignant-growth-in-epithelial-tissues
#9
Mariana Muzzopappa, Lada Murcia, Marco Milán
Interactions between cells bearing oncogenic mutations and the surrounding microenvironment, and cooperation between clonally distinct cell populations, can contribute to the growth and malignancy of epithelial tumors. The genetic techniques available in Drosophila have contributed to identify important roles of the TNF-α ligand Eiger and mitogenic molecules in mediating these interactions during the early steps of tumor formation. Here we unravel the existence of a tumor-intrinsic-and microenvironment-independent-self-reinforcement mechanism that drives tumor initiation and growth in an Eiger-independent manner...
August 29, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28754838/the-chromatin-remodeling-bap-complex-limits-tumor-promoting-activity-of-the-hippo-pathway-effector-yki-to-prevent-neoplastic-transformation-in-drosophila-epithelia
#10
Shilin Song, Héctor Herranz, Stephen M Cohen
SWI/SNF chromatin remodeling complexes are mutated in many human cancers. In this report we make use of a Drosophila genetic model for epithelial tumor formation to explore the tumor suppressive role of SWI/SNF complex proteins. Members of the BAP complex exhibit tumor suppressor activity in tissue overexpressing the Yorkie (Yki) proto-oncogene, but not in tissue overexpressing EGFR. The BAP complex has been reported to serve as a Yki-binding cofactor to support Yki target expression. However, we observed that depletion of BAP leads to ectopic expression of Yki targets both autonomously and non-autonomously, suggesting additional indirect effects...
July 28, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28750888/the-tumor-suppressor-cyld-controls-epithelial-morphogenesis-and-homeostasis-by-regulating-mitotic-spindle-behavior-and-adherens-junction-assembly
#11
Wei Xie, Yunfan Yang, Siqi Gao, Ting Song, Yuhan Wu, Dengwen Li, Min Liu, Jun Zhou
Epithelial morphogenesis and homeostasis are essential for animal development and tissue regeneration, and epithelial disorganization is associated with developmental disorders and tumorigenesis. However, the molecular mechanisms that contribute to the morphogenesis and homeostasis of the epithelium remain elusive. Herein, we report a novel role for the cylindromatosis (CYLD) tumor suppressor in these events. Our results show that CYLD depletion disrupts epithelial organization in both Drosophila egg chambers and mouse skin and intestinal epithelia...
July 20, 2017: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/28743793/animal-models-of-men-1
#12
Hermine Mohr, Natalia S Pellegata
Animal models of cancer have been instrumental in advancing our understanding of the biology of tumor initiation and progression, in studying gene function, and in performing preclinical studies aimed at testing novel therapies. Several animal models of the MEN1 syndrome have been generated in different organisms by introducing loss-of-function mutations in the orthologues of the human MEN1 gene. In this review, we will discuss MEN1 and MEN1-like models in Drosophila, mice and rats. These model systems with their specific advantages and limitations have contributed to elucidate the function of Menin in tumorigenesis, which turned out to be remarkably conserved from flies to mammals, as well as the biology of the disease...
July 25, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28718438/tissue-intrinsic-tumor-hotspots-terroir-for-tumorigenesis
#13
REVIEW
Yoichiro Tamori, Wu-Min Deng
Epithelial tissues are highly organized systems with a remarkable homeostatic ability to maintain morphology through regulation of cellular proliferation and tissue integrity. This robust self-organizing system is progressively disrupted during tumor development. Recent studies of conserved tumor-suppressor genes in Drosophila showed how protumor cells deviate from the robustly organized tissue microenvironment to take the first steps into becoming aggressive tumors. Here we review the 'tumor hotspot' hypothesis that explains how the tissue-intrinsic local microenvironment has a pivotal role in the initial stage of tumorigenesis in Drosophila epithelia and discuss comparable mechanisms in mammalian tissues...
April 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28712876/drosophila-sce-dring-e3-ligase-inhibits-apoptosis-in-a-dp53-dependent-manner
#14
Carolina J Simoes da Silva, Sol Fereres, Rocío Simón, Ana Busturia
The Polycomb group (PcG) of proteins control developmental gene silencing and are highly conserved between flies and mammals. PcG proteins function by controlling post-translational modification of histones, such as ubiquitylation, which impacts chromatin compaction and thus gene transcription. Changes in PcG cellular levels have drastic effects on organismal development and are involved in the generation of human pathologies such as cancer. However, the mechanisms controlling their levels of expression and their physiological effects are only partially understood...
September 1, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28708826/intestinal-stem-cell-overproliferation-resulting-from-inactivation-of-the-apc-tumor-suppressor-requires-the-transcription-cofactors-earthbound-and-erect-wing
#15
Ai Tian, Hassina Benchabane, Zhenghan Wang, Chloe Zimmerman, Nan Xin, Jessica Perochon, Gabriela Kalna, Owen J Sansom, Chao Cheng, Julia B Cordero, Yashi Ahmed
Wnt/β-catenin signal transduction directs intestinal stem cell (ISC) proliferation during homeostasis. Hyperactivation of Wnt signaling initiates colorectal cancer, which most frequently results from truncation of the tumor suppressor Adenomatous polyposis coli (APC). The β-catenin-TCF transcription complex activates both the physiological expression of Wnt target genes in the normal intestinal epithelium and their aberrantly increased expression in colorectal tumors. Whether mechanistic differences in the Wnt transcription machinery drive these distinct levels of target gene activation in physiological versus pathological states remains uncertain, but is relevant for the design of new therapeutic strategies...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28658615/pp6-disruption-synergizes-with-oncogenic-ras-to-promote-jnk-dependent-tumor-growth-and-invasion
#16
Xianjue Ma, Jin-Yu Lu, Yongli Dong, Daming Li, Juan N Malagon, Tian Xu
RAS genes are frequently mutated in cancers, yet an effective treatment has not been developed, partly because of an incomplete understanding of signaling within Ras-related tumors. To address this, we performed a genetic screen in Drosophila, aiming to find mutations that cooperate with oncogenic Ras (Ras(V12)) to induce tumor overgrowth and invasion. We identified fiery mountain (fmt), a regulatory subunit of the protein phosphatase 6 (PP6) complex, as a tumor suppressor that synergizes with Ras(V12) to drive c-Jun N-terminal kinase (JNK)-dependent tumor growth and invasiveness...
June 27, 2017: Cell Reports
https://www.readbyqxmd.com/read/28648883/molecular-cloning-and-functional-analysis-of-tumor-necrosis-factor-receptor-associated-factor-6-traf6-in-crossastrea-gigas
#17
Fan Mao, Jun Li, Yuehuan Zhang, Zhiming Xiang, Yang Zhang, Ziniu Yu
Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been demonstrated to be a key signaling molecule involved in adaptive and innate immunity. In this study, we obtained the full length CgTRAF6 cDNA and analyzed the characteristics of the ORF and the peptide sequence in Crassostrea gigas. The deduced protein sequence of CgTRAF6 includes a conserved C-terminal TRAF domain following the RING and the zinc finger domain. The TRAF domain is composed of coiled-coil TRAF-N and MATH (meprin and TRAF-C homology) subdomains...
June 23, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28620760/notch-an-interactive-player-in-neurogenesis-and-disease
#18
REVIEW
Runrui Zhang, Anna Engler, Verdon Taylor
Notch signaling is evolutionarily conserved from Drosophila to human. It plays critical roles in neural stem cell maintenance and neurogenesis in the embryonic brain as well as in the adult brain. Notch functions greatly depend on careful regulation and cross-talk with other regulatory mechanisms. Deregulation of Notch signaling is involved in many neurodegenerative diseases and brain disorders. Here, we summarize the fundamental role of Notch in neuronal development and specification and discuss how epigenetic regulation and pathway cross-talk contribute to Notch function...
June 15, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28620086/a-genetic-screen-reveals-an-unexpected-role-for-yorkie-signaling-in-jak-stat-dependent-hematopoietic-malignancies-in-drosophila-melanogaster
#19
Abigail M Anderson, Alessandro A Bailetti, Elizabeth Rodkin, Atish De, Erika A Bach
A gain-of-function mutation in the tyrosine kinase JAK2 (JAK2(V617F) ) causes human myeloproliferative neoplasms (MPNs). These patients present with high numbers of myeloid lineage cells and have numerous complications. Since current MPN therapies are not curative, there is a need to find new regulators and targets of Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling that may represent additional clinical interventions . Drosophila melanogaster offers a low complexity model to study MPNs as JAK/STAT signaling is simplified with only one JAK [Hopscotch (Hop)] and one STAT (Stat92E)...
August 7, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28619822/cop9-signalosome-subunits-protect-capicua-from-mapk-dependent-and-independent-mechanisms-of-degradation
#20
Annabelle Suisse, DanQing He, Kevin Legent, Jessica E Treisman
The COP9 signalosome removes Nedd8 modifications from the Cullin subunits of ubiquitin ligase complexes, reducing their activity. Here, we show that mutations in the Drosophila COP9 signalosome subunit 1b (CSN1b) gene increase the activity of ubiquitin ligases that contain Cullin 1. Analysis of CSN1b mutant phenotypes revealed a requirement for the COP9 signalosome to prevent ectopic expression of Epidermal growth factor receptor (EGFR) target genes. It does so by protecting Capicua, a transcriptional repressor of EGFR target genes, from EGFR pathway-dependent ubiquitylation by a Cullin 1/SKP1-related A/Archipelago E3 ligase and subsequent proteasomal degradation...
July 15, 2017: Development
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