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https://www.readbyqxmd.com/read/29035383/extracellular-nme-proteins-a-player-or-a-bystander
#1
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
https://www.readbyqxmd.com/read/29017815/rna-polymerase-ii-pausing-and-transcriptional-regulation-of-the-hsp70-expression
#2
REVIEW
Heeyoun Bunch
Heat-shock proteins (HSPs) belong to the chaperone protein family whose expression is induced by different stresses including heat-shock. In response to the extracellular or intrinsic stimuli and stresses, HSPs play important roles in the maintenance of cellular homeostasis. HSP70, a major HSP protein (molecular weight, 70 KDa), regulates diverse cellular pathways including protein quality control, translation, immune response, and cancer survival. As a critical cellular defense system to minimize damages from cellular stresses, HSP70 expression and transcriptional activation are rapidly regulated, mainly through the action of a transcription activator, Heat shock factor 1 (HSF1)...
October 3, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28983086/can-intestinal-microbiota-be-associated-with-non-intestinal-cancers
#3
Camille Jacqueline, Lionel Brazier, Dominique Faugère, François Renaud, Frédéric Thomas, Benjamin Roche
While the role of intestinal microbiota is increasingly recognized in the etiology of digestive cancers, its effects on the development of cancer in other parts of the body have been little studied. Through new-generation sequencing, we aimed to identify an association between the structure of intestinal microbiota and the presence of eye disc tumor in Drosophila larvae. First, we observed a parental effect on the diversity and structure of bacterial communities. Second, we identified a bacterial signature (at the family level) of cancer: cancerous larvae host a significantly lower relative abundance of Bacillaceae than individuals that did not develop the tumor...
October 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28974715/human-cancer-cells-signal-their-competitive-fitness-through-myc-activity
#4
Simone Di Giacomo, Manuela Sollazzo, Dario de Biase, Moira Ragazzi, Paola Bellosta, Annalisa Pession, Daniela Grifoni
MYC-mediated cell competition is a cell-cell interaction mechanism known to play an evolutionary role during development from Drosophila to mammals. Cells expressing low levels of MYC, called losers, are committed to die by nearby cells with high MYC activity, called winners, that overproliferate to compensate for cell loss, so that the fittest cells be selected for organ formation. Given MYC's consolidated role in oncogenesis, cell competition is supposed to be relevant to cancer, but its significance in human malignant contexts is largely uncharacterised...
October 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28966044/hdac6-suppresses-age-dependent-ectopic-fat-accumulation-by-maintaining-the-proteostasis-of-plin2-in-drosophila
#5
Yan Yan, Hao Wang, Minling Hu, Lifen Jiang, Yang Wang, Pingsheng Liu, Xuehong Liang, Jiyong Liu, Changqing Li, Anya Lindström-Battle, Sin Man Lam, Guanghou Shui, Wu-Min Deng, Renjie Jiao
Age-dependent ectopic fat accumulation (EFA) in animals contributes to the progression of tissue aging and diseases such as obesity, diabetes, and cancer. However, the primary causes of age-dependent EFA remain largely elusive. Here, we characterize the occurrence of age-dependent EFA in Drosophila and identify HDAC6, a cytosolic histone deacetylase, as a suppressor of EFA. Loss of HDAC6 leads to significant age-dependent EFA, lipid composition imbalance, and reduced animal longevity on a high-fat diet. The EFA and longevity phenotypes are ameliorated by a reduction of the lipid-droplet-resident protein PLIN2...
October 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28963499/apontic-directly-activates-hedgehog-and-cyclin-e-for-proper-organ-growth-and-patterning
#6
Xian-Feng Wang, Yang Shen, Qian Cheng, Chong-Lei Fu, Zi-Zhang Zhou, Susumu Hirose, Qing-Xin Liu
Hedgehog (Hh) signaling pathway and Cyclin E are key players in cell proliferation and organ development. Hyperactivation of hh and cyclin E has been linked to several types of cancer. However, coordination of the expression of hh and cyclin E was not well understood. Here we show that an evolutionarily conserved transcription factor Apontic (Apt) directly activates hh and cyclin E through its binding site in the promoter regions of hh and cyclin E. This Apt-dependent proper expression of hh and cyclin E is required for cell proliferation and development of the Drosophila wing...
September 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28947795/stable-mob1-interaction-with-hippo-mst-is-not-essential-for-development-and-tissue-growth-control
#7
Yavuz Kulaberoglu, Kui Lin, Maxine Holder, Zhongchao Gai, Marta Gomez, Belul Assefa Shifa, Merdiye Mavis, Lily Hoa, Ahmad A D Sharif, Celia Lujan, Ewan St John Smith, Ivana Bjedov, Nicolas Tapon, Geng Wu, Alexander Hergovich
The Hippo tumor suppressor pathway is essential for development and tissue growth control, encompassing a core cassette consisting of the Hippo (MST1/2), Warts (LATS1/2), and Tricornered (NDR1/2) kinases together with MOB1 as an important signaling adaptor. However, it remains unclear which regulatory interactions between MOB1 and the different Hippo core kinases coordinate development, tissue growth, and tumor suppression. Here, we report the crystal structure of the MOB1/NDR2 complex and define key MOB1 residues mediating MOB1's differential binding to Hippo core kinases, thereby establishing MOB1 variants with selective loss-of-interaction...
September 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28945745/p53-dependent-programmed-necrosis-controls-germ-cell-homeostasis-during-spermatogenesis
#8
Francesco Napoletano, Benjamin Gibert, Keren Yacobi-Sharon, Stéphane Vincent, Clémentine Favrot, Patrick Mehlen, Victor Girard, Margaux Teil, Gilles Chatelain, Ludivine Walter, Eli Arama, Bertrand Mollereau
The importance of regulated necrosis in pathologies such as cerebral stroke and myocardial infarction is now fully recognized. However, the physiological relevance of regulated necrosis remains unclear. Here, we report a conserved role for p53 in regulating necrosis in Drosophila and mammalian spermatogenesis. We found that Drosophila p53 is required for the programmed necrosis that occurs spontaneously in mitotic germ cells during spermatogenesis. This form of necrosis involved an atypical function of the initiator caspase Dronc/Caspase 9, independent of its catalytic activity...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28942426/rapid-dna-synthesis-during-early-drosophila%C3%A2-embryogenesis-is-sensitive-to-maternal-humpty-dumpty-protein-function
#9
Shera Lesly, Jennifer L Bandura, Brian R Calvi
Problems with DNA replication cause cancer and developmental malformations. It is not fully understood how DNA replication is coordinated with development and perturbed in disease. We had previously identified the Drosophila gene humpty dumpty (hd) and showed that null alleles cause incomplete DNA replication, tissue undergrowth, and lethality. Animals homozygous for the missense allele, hd(272-9) , were viable, but adult females had impaired amplification of eggshell protein genes in the ovary, resulting in the maternal effects of thin eggshells and embryonic lethality...
September 23, 2017: Genetics
https://www.readbyqxmd.com/read/28933588/death-by-over-eating-the-gaucher-disease-associated-gene-gba1-identified-in-a-screen-for-mediators-of-autophagic-cell-death-is-necessary-for-developmental-cell-death-in-drosophila-midgut
#10
Santosh K Dasari, Eyal Schejter, Shani Bialik, Aya Shkedy, Vered Levin-Salomon, Smadar Levin-Zaidman, Adi Kimchi
Autophagy is critical for homeostasis and cell survival during stress, but can also lead to cell death, a little understood process that has been shown to contribute to developmental cell death in lower model organisms, and to human cancer cell death. We recently reported (1) on our thorough molecular and morphologic characterization of an autophagic cell death system involving resveratrol treatment of lung carcinoma cells. To gain mechanistic insight into this death program, we performed a signalome-wide RNAi screen for genes whose functions are necessary for resveratrol-induced death...
September 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28930984/high-fat-diet-feeding-and-high-throughput-triacylglyceride-assay-in-drosophila-melanogaster
#11
Soda Balla Diop, Ryan T Birse, Rolf Bodmer
Heart disease is the number one cause of human death worldwide. Numerous studies have shown strong connections between obesity and cardiac malfunction in humans, but more tools and research efforts are needed to better elucidate the mechanisms involved. For over a century, the genetically highly tractable model of Drosophila has been instrumental in the discovery of key genes and molecular pathways that proved to be highly conserved across species. Many biological processes and disease mechanisms are functionally conserved in the fly, such as development (e...
September 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28927532/beyond-mouse-cancer-models-three-dimensional-human-relevant-in-vitro-and-non-mammalian-in-vivo-models-for-photodynamic-therapy
#12
REVIEW
Malgorzata Kucinska, Marek Murias, Patrycja Nowak-Sliwinska
The proper design of experiments is a critical step for each study in order to obtain reproducible and reliable data. Taking into account constant competitiveness in the quickly developing biomedical sciences and the availability of sophisticated techniques, the choice and establishment of an experimental model system are essential for a successful research project. Currently, various sophisticated in vitro and in vivo models are being designed and developed in order to replace the use of mammalian models to investigate the mechanisms of action, activity and properties of novel compounds or treatment modalities...
July 2017: Mutation Research
https://www.readbyqxmd.com/read/28920944/the-dosage-dependent-effect-exerted-by-the-nm23-h1-h2-homolog-ndk-1-on-distal-tip-cell-migration-in-c-elegans
#13
Zsolt Farkas, Luca Fancsalszky, Éva Saskői, Alexandra Gráf, Krisztián Tárnok, Anil Mehta, Krisztina Takács-Vellai
Abnormal regulation of cell migration and altered rearrangement of the cytoskeleton are fundamental properties of metastatic cells. The first identified metastasis suppressor NM23-H1, which displays nucleoside-diphosphate kinase (NDPK) activity is involved in these processes. NM23-H1 inhibits the migratory and invasive potential of some cancer cells. Correspondingly, numerous invasive cancer cell lines (eg, breast, colon, oral, hepatocellular carcinoma, and melanoma) display low endogenous NM23 levels. In this review, we summarize mechanisms, which are linked to the anti-metastatic activity of NM23...
September 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28917942/in-vivo-and-in-vitro-testing-of-native-%C3%AE-conotoxins-from-the-injected-venom-of-conus-purpurascens
#14
REVIEW
Mickelene F Hoggard, Alena M Rodriguez, Herminsul Cano, Evan Clark, Han-Shen Tae, David J Adams, Tanja A Godenschwege, Frank Marí
α-Conotoxins inhibit nicotinic acetylcholine receptors (nAChRs) and are used as probes to study cholinergic pathways in vertebrates. Model organisms, such as Drosophila melanogaster, express nAChRs in their CNS that are suitable to investigate the neuropharmacology of α-conotoxins in vivo. Here we report the paired nanoinjection of native α-conotoxin PIA and two novel α-conotoxins, PIC and PIC[O7], from the injected venom of Conus purpurascens and electrophysiological recordings of their effects on the giant fiber system (GFS) of D...
September 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28912546/phosphoenolpyruvate-carboxykinase-maintains-glycolysis-driven-growth-in-drosophila-tumors
#15
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/28887318/ubcd1-regulates-hedgehog-signaling-by-directly-modulating-ci-ubiquitination-and-processing
#16
Chenyu Pan, Yue Xiong, Xiangdong Lv, Yuanxin Xia, Shuo Zhang, Hao Chen, Jialin Fan, Wenqing Wu, Feng Liu, Hailong Wu, Zhaocai Zhou, Lei Zhang, Yun Zhao
The Hh pathway controls many morphogenetic processes in metazoans and plays important roles in numerous pathologies and in cancer. Hh signaling is mediated by the activity of the Gli/Ci family of transcription factors. Several studies in Drosophila have shown that ubiquitination by the ubiquitin E3 ligases Slimb and Rdx(Hib) plays a crucial role in controlling Ci stability dependent on the levels of Hh signals. If Hh levels are low, Slimb adds K11- and K48-linked poly-ubiquitin chains on Ci resulting in partial degradation...
September 8, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28882225/animal-models-to-study-microrna-function
#17
Arpita S Pal, Andrea L Kasinski
The discovery of the microRNAs, lin-4 and let-7 as critical mediators of normal development in Caenorhabditis elegans and their conservation throughout evolution has spearheaded research toward identifying novel roles of microRNAs in other cellular processes. To accurately elucidate these fundamental functions, especially in the context of an intact organism, various microRNA transgenic models have been generated and evaluated. Transgenic C. elegans (worms), Drosophila melanogaster (flies), Danio rerio (zebrafish), and Mus musculus (mouse) have contributed immensely toward uncovering the roles of multiple microRNAs in cellular processes such as proliferation, differentiation, and apoptosis, pathways that are severely altered in human diseases such as cancer...
2017: Advances in Cancer Research
https://www.readbyqxmd.com/read/28877471/kif5b-ret-oncoprotein-signals-through-a-multi-kinase-signaling-hub
#18
Tirtha Kamal Das, Ross Leigh Cagan
Gene fusions are increasingly recognized as important cancer drivers. The KIF5B-RET gene has been identified as a primary driver in a subset of lung adenocarcinomas. Targeting human KIF5B-RET to epithelia in Drosophila directed multiple aspects of transformation, including hyperproliferation, epithelial-to-mesenchymal transition, invasion, and extension of striking invadopodia-like processes. The KIF5B-RET-transformed human bronchial cell line showed similar aspects of transformation, including invadopodia-like processes...
September 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28868955/neurogenetics-of-drosophila-circadian-clock-expect-the-unexpected
#19
Patricia Jarabo, Francisco A Martin
Daily biological rhythms (i.e. circadian) are a fundamental part of animal behavior. Numerous reports have shown disruptions of the biological clock in neurodegenerative disorders and cancer. In the latter case, only recently we have gained insight into the molecular mechanisms. After 45 years of intense study of the circadian rhtythms, we find surprising similarities among species on the molecular clock that governs biological rhythms. Indeed, Drosophila is one of the most widely used models in the study of chronobiology...
September 4, 2017: Journal of Neurogenetics
https://www.readbyqxmd.com/read/28859623/ancient-human-mirnas-are-more-likely-to-have-broad-functions-and-disease-associations-than-young-mirnas
#20
Vir D Patel, John A Capra
BACKGROUND: microRNAs (miRNAs) are essential to the regulation of gene expression in eukaryotes, and improper expression of miRNAs contributes to hundreds of diseases. Despite the essential functions of miRNAs, the evolutionary dynamics of how they are integrated into existing gene regulatory and functional networks is not well understood. Knowledge of the origin and evolutionary history a gene has proven informative about its functions and disease associations; we hypothesize that incorporating the evolutionary origins of miRNAs into analyses will help resolve differences in their functional dynamics and how they influence disease...
August 31, 2017: BMC Genomics
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