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https://www.readbyqxmd.com/read/29348326/symmetry-from-asymmetry-or-asymmetry-from-symmetry
#1
Elizabeth W Kahney, Rajesh Ranjan, Ryan J Gleason, Xin Chen
The processes of DNA replication and mitosis allow the genetic information of a cell to be copied and transferred reliably to its daughter cells. However, if DNA replication and cell division were always performed in a symmetric manner, the result would be a cluster of tumor cells instead of a multicellular organism. Therefore, gaining a complete understanding of any complex living organism depends on learning how cells become different while faithfully maintaining the same genetic material. It is well recognized that the distinct epigenetic information contained in each cell type defines its unique gene expression program...
January 18, 2018: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/29348307/non-mammalian-models-of-multiple-endocrine-neoplasia-type-2
#2
REVIEW
Tirtha K Das, Ross L Cagan
Twenty-five years ago, RET was identified as the primary driver of multiple endocrine neoplasia type 2 (MEN2) syndrome. MEN2 is characterized by several transformation events including pheochromocytoma, parathyroid adenoma and, especially penetrant, medullary thyroid carcinoma (MTC). Overall, MTC is a rare but aggressive type of thyroid cancer for which no effective treatment currently exists. Surgery, radiation, radioisotope treatment and chemotherapeutics have all shown limited success, and none of these approaches have proven durable in advanced disease...
February 2018: Endocrine-related Cancer
https://www.readbyqxmd.com/read/29323461/n-benzyl-substitution-of-polyhydroxypyrrolidines-the-way-to-selective-inhibitors-of-golgi-%C3%AE-mannosidase-ii
#3
Sergej Šesták, Maroš Bella, Tomáš Klunda, Soňa Gurská, Petr Džubák, Florian Wöls, Iain Bh Wilson, Vladimir Sladek, Marián Hajdúch, Monika Polakova, Juraj Kóňa
Inhibition of biosynthesis of complex N-glycans in Golgi apparatus influence progress of tumor growth and metastasis. Golgi α-mannosidase II (GMII) has become a therapeutic target for a drug with anticancer activities. One critical task for successful application GMII drugs in medicine treatment is to reduce their unwanted co-inhibition with lysosomal α-mannosidase (LMan) by which suffer all known potent GMII inhibitors. A series of novel N-substituted polyhydroxypyrrolidines was synthesized and tested with modeled GH38 α-mannosidases from Drosophila melanogaster (GMIIb and LManII)...
January 11, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29317532/alkals-are-in-vivo-ligands-for-alk-family-receptor-tyrosine-kinases-in-the-neural-crest-and-derived-cells
#4
Andrey Fadeev, Patricia Mendoza-Garcia, Uwe Irion, Jikui Guan, Kathrin Pfeifer, Stephanie Wiessner, Fabrizio Serluca, Ajeet Pratap Singh, Christiane Nüsslein-Volhard, Ruth H Palmer
Mutations in anaplastic lymphoma kinase (ALK) are implicated in somatic and familial neuroblastoma, a pediatric tumor of neural crest-derived tissues. Recently, biochemical analyses have identified secreted small ALKAL proteins (FAM150, AUG) as potential ligands for human ALK and the related leukocyte tyrosine kinase (LTK). In the zebrafish Danio rerio, DrLtk, which is similar to human ALK in sequence and domain structure, controls the development of iridophores, neural crest-derived pigment cells. Hence, the zebrafish system allows studying Alk/Ltk and Alkals involvement in neural crest regulation in vivo...
January 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29312571/systematic-analysis-reveals-tumor-enhancing-and-suppressing-micrornas-in-drosophila-epithelial-tumors
#5
Zhiqiang Shu, Yi-Chun Huang, William H Palmer, Yoichiro Tamori, Gengqiang Xie, Hui Wang, Nan Liu, Wu-Min Deng
Despite their emergence as an important class of noncoding RNAs involved in cancer cell transformation, invasion, and migration, the precise role of microRNAs (miRNAs) in tumorigenesis remains elusive. To gain insights into how miRNAs contribute to primary tumor formation, we conducted an RNA sequencing (RNA-Seq) analysis of Drosophila wing disc epithelial tumors induced by knockdown of a neoplastic tumor-suppressor gene (nTSG) lethal giant larvae (lgl), combined with overexpression of an active form of oncogene Ras (RasV12 ), and identified 51 mature miRNAs that changed significantly in tumorous discs...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29281929/protective-effect-of-aspirin-against-mitomycin-c-induced-carcinogenicity-assessed-by-the-test-for-detection-of-epithelial-tumor-clones-warts-in-drosophila-melanogaster
#6
Victor Constante Oliveira, Sarah Alves Rodrigues Constante, Lorena Polloni, Priscila Capelari Orsolin, Rosiane Gomes Silva-Oliveira, Nayane Moreira Machado, Robson José de Oliveira-Júnior, Júlio César Nepomuceno
The present study assessed the protective effect of aspirin against carcinogenicity induced by mitomycin C (MMC) by the test for detection of warts/epithelial tumor clones in Drosophila melanogaster. Larvae were treated with different concentrations of aspirin alone (10, 20 or 40 mg/mL) or aspirin in association with MMC. MMC and ultrapure water were employed as the positive and negative control, respectively. Antioxidant activity was determined using the DPPH method. For performing cytotoxicity assay on HeLa cells, the aspirin concentrations used ranged from 200 mmol/L to 3,125 mmol/L...
December 27, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/29274400/conditional-mitotimer-reporter-mice-for-assessment-of-mitochondrial-structure-oxidative-stress-and-mitophagy
#7
Rebecca J Wilson, Joshua C Drake, Di Cui, Mei Zhang, Heather M Perry, Jennifer A Kashatus, Christine M Kusminski, Philipp E Scherer, David F Kashatus, Mark D Okusa, Zhen Yan
Assessment of structural and functional changes of mitochondria is vital for biomedical research as mitochondria are the power plants essential for biological processes and tissue/organ functions. Others and we have developed a novel reporter gene, pMitoTimer, which codes for a redox sensitive mitochondrial targeted protein that switches from green fluorescence protein (GFP) to red fluorescent protein (DsRed) when oxidized. It has been shown in transfected cells, transgenic C. elegans and Drosophila m., as well as somatically transfected adult skeletal muscle that this reporter gene allows quantifiable assessment of mitochondrial structure, oxidative stress, and lysosomal targeting of mitochondria-containing autophagosomes...
December 20, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29239688/compromising-asymmetric-stem-cell-division-in-drosophila-central-brain-revisiting-the-connections-with-tumorigenesis
#8
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/29208636/homeodomain-interacting-protein-kinase-promotes-tumorigenesis-and-metastatic-cell-behavior
#9
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/29199019/widespread-rewiring-of-genetic-networks-upon-cancer-signaling-pathway-activation
#10
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/29191977/the-tumor-suppressor-brat-controls-neuronal-stem-cell-lineages-by-inhibiting-deadpan-and-zelda
#11
Ilka Reichardt, François Bonnay, Victoria Steinmann, Inga Loedige, Thomas R Burkard, Gunter Meister, Juergen A Knoblich
The TRIM-NHL protein Brain tumor (Brat) acts as a tumor suppressor in the Drosophila brain, but how it suppresses tumor formation is not completely understood. Here, we combine temperature-controlled brat RNAi with transcriptome analysis to identify the immediate Brat targets in Drosophila neuroblasts. Besides the known target Deadpan (Dpn), our experiments identify the transcription factor Zelda (Zld) as a critical target of Brat. Our data show that Zld is expressed in neuroblasts and required to allow re-expression of Dpn in transit-amplifying intermediate neural progenitors...
November 30, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29185419/activation-of-discs-large-by-apkc-aligns-the-mitotic-spindle-to-the-polarity-axis-during-asymmetric-cell-division
#12
Ognjen Golub, Brett Wee, Rhonda A Newman, Nicole M Paterson, Kenneth E Prehoda
Asymmetric division generates cellular diversity by producing daughter cells with different fates. In animals, the mitotic spindle aligns with Par complex polarized fate determinants, ensuring that fate determinant cortical domains are bisected by the cleavage furrow. Here, we investigate the mechanisms that couple spindle orientation to polarity during asymmetric cell division of Drosophila neuroblasts. We find that the tumor suppressor Discs large (Dlg) links the Par complex component atypical Protein Kinase C (aPKC) to the essential spindle orientation factor GukHolder (GukH)...
November 29, 2017: ELife
https://www.readbyqxmd.com/read/29183982/improved-detection-of-synthetic-lethal-interactions-in-drosophila-cells-using-variable-dose-analysis-vda
#13
Benjamin E Housden, Zhongchi Li, Colleen Kelley, Yuanli Wang, Yanhui Hu, Alexander J Valvezan, Brendan D Manning, Norbert Perrimon
Synthetic sick or synthetic lethal (SS/L) screens are a powerful way to identify candidate drug targets to specifically kill tumor cells, but this approach generally suffers from low consistency between screens. We found that many SS/L interactions involve essential genes and are therefore detectable within a limited range of knockdown efficiency. Such interactions are often missed by overly efficient RNAi reagents. We therefore developed an assay that measures viability over a range of knockdown efficiency within a cell population...
December 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29154825/the-scf-ubiquitin-ligase-slimb-controls-nerfin-1-turnover-in-drosophila
#14
Xiaohui Lin, Feng Wang, Yuanpei Li, Chaojun Zhai, Guiping Wang, Xiaoting Zhang, Yang Gao, Tao Yi, Dan Sun, Shian Wu
The C2H2 type zinc-finger transcription factor Nerfin-1 expresses dominantly in Drosophila nervous system and plays an important role in early axon guidance decisions and preventing neurons dedifferentiation. Recently, increasing reports indicated that INSM1 (homologue to nerfin-1 in mammals) is a useful marker for prognosis of neuroendocrine tumors. The dynamic expression of Nerfin-1 is regulated post-transcriptionally by multiple microRNAs; however, its post-translational regulation is still unclear. Here we showed that the protein turnover of Nerfin-1 is regulated by Slimb, the substrate adaptor of SCF(Slimb) ubiquitin ligase complex...
November 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29152127/minocycline-treatment-increases-resistance-to-oxidative-stress-and-extends-lifespan-in-drosophila-via-foxo
#15
Gang Jun Lee, Jin Ju Lim, Seogang Hyun
Minocycline is a semi-synthetic tetracycline derivative antibiotic that has received increasing attention for its non-antibiotic properties, mainly anti-inflammatory, tumor-suppressive, and neuroprotective effects. Drosophila is a widely used genetically tractable model organism for studying organismal aging by virtue of its short lifespan and ease of cultivation. In this study, we examined the effects of minocycline on Drosophila lifespan and its associated traits. Minocycline-supplemented food significantly extended lifespan in both Canton S and w(1118) Drosophila strains...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29149408/function-of-translationally-controlled-tumor-protein-in-organ-growth-lessons-from-drosophila-studies
#16
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
#17
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/29124738/transcripts-immunoprecipitated-with-sxl-protein-in-primordial-germ-cells-of-drosophila-embryos
#18
Ryoma Ota, Shumpei Morita, Masanao Sato, Shuji Shigenobu, Makoto Hayashi, Satoru Kobayashi
In Drosophila, Sex lethal (Sxl), an RNA binding protein, is required for induction of female sexual identity in both somatic and germline cells. Although the Sxl-dependent feminizing pathway in the soma was previously elucidated, the downstream targets for Sxl in the germline remained elusive. To identify these target genes, we selected transcripts associated with Sxl in primordial germ cells (PGCs) of embryos using RNA immunoprecipitation coupled to sequencing (RIP-seq) analysis. A total of 308 transcripts encoded by 282 genes were obtained...
November 10, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/29107812/proteolytic-maturation-of-drosophila-neuroligin-3-by-tumor-necrosis-factor-%C3%AE-converting-enzyme-in-the-nervous-system
#19
Jun Wu, Nana Tao, Yao Tian, Guanglin Xing, Huihui Lv, Junhai Han, Chengqi Lin, Wei Xie
BACKGROUND: The functions of autism-associated Neuroligins (Nlgs) are modulated by their post-translational modifications, such as proteolytic cleavage. A previous study has shown that there are different endogenous forms of DNlg3 in Drosophila, indicating it may undergo proteolytic processing. However, the molecular mechanism underlying DNlg3 proteolytic processing is unknown. Here, we report a novel proteolytic mechanism that is essential for DNlg3 maturation and function in the nervous system...
October 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29105522/orb2-as-modulator-of-brat-and-their-role-at-the-neuromuscular-junction
#20
Elena Santana, Sergio Casas-Tintó
How synapses are built and dismantled is a central question in neurobiology. A wide range of proteins and processes from gene transcription to protein degradation are involved. Orb2 regulates mRNA translation depending on its monomeric or oligomeric state to modulate nervous system development and memory. Orb2 is expressed in Drosophila larval brain and neuromuscular junction (NMJ), Orb2 knockdown causes a reduction of synapse number and defects in neuronal morphology. Brain tumor (Brat) is an Orb2 target; it is expressed in larval brain related with cell growth and proliferation...
November 6, 2017: Journal of Neurogenetics
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