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https://www.readbyqxmd.com/read/29677182/foxo-restricts-growth-and-differentiation-of-cells-with-elevated-torc1-activity-under-nutrient-restriction
#1
Katarzyna Nowak, Avantika Gupta, Hugo Stocker
TORC1, a central regulator of cell survival, growth, and metabolism, is activated in a variety of cancers. Loss of the tumor suppressors PTEN and Tsc1/2 results in hyperactivation of TORC1. Tumors caused by the loss of PTEN, but not Tsc1/2, are often malignant and have been shown to be insensitive to nutrient restriction (NR). In Drosophila, loss of PTEN or Tsc1 results in hypertrophic overgrowth of epithelial tissues under normal nutritional conditions, and an enhanced TORC1-dependent hyperplastic overgrowth of PTEN mutant tissue under NR...
April 20, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29661224/notch-signals-modulate-lgl-mediated-tumorigenesis-by-the-activation-of-jnk-signaling
#2
Maimuna Sali Paul, Ankita Singh, Debdeep Dutta, Mousumi Mutsuddi, Ashim Mukherjee
OBJECTIVES: Oncogenic potential of Notch signaling and its cooperation with other factors to affect proliferation are widely established. Notch exhibits a cooperative effect with loss of a cell polarity gene, scribble to induce neoplastic overgrowth. Oncogenic Ras also show cooperative effect with loss of cell polarity genes such as scribble (scrib), lethal giant larvae (lgl) and discs large to induce neoplastic overgrowth and invasion. Our study aims at assessing the cooperation of activated Notch with loss of function of lgl in tumor overgrowth, and the mode of JNK signaling activation in this context...
April 16, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29653289/src-activation-decouples-cell-division-orientation-from-cell-geometry-in-mammalian-cells
#3
Xiaoyan Sun, Hongsheng Qi, Xiuzhen Zhang, Li Li, Jiaping Zhang, Qunli Zeng, George S Laszlo, Bo Wei, Tianhong Li, Jianxin Jiang, Alex Mogilner, Xiaobing Fu, Min Zhao
Orientation of cell division plane plays a crucial role in morphogenesis and regeneration. Misoriented cell division underlies many important diseases, such as cancer. Studies with Drosophila and C. elegance models show that Src, a proto-oncogene tyrosine-protein kinase, is a critical regulator of this aspect of mitosis. However, the role for Src in controlling cell division orientation in mammalian cells is not well understood. Using genetic and pharmacological approaches and two extracellular signals to orient cell division, we demonstrated a critical role for Src...
April 3, 2018: Biomaterials
https://www.readbyqxmd.com/read/29644870/a-novel-polyphenolic-prebiotic-and-probiotic-formulation-have-synergistic-effects-on-the-gut-microbiota-influencing-drosophila-melanogaster-physiology
#4
Susan Westfall, Nikita Lomis, Satya Prakash
The gut microbiota is a vast community of synergistic bacterial species providing health benefits to the host. Imbalances in the gut microbiota (dysbiosis) due to diet, antibiotic use, age and stress contribute to disease development including diabetes, obesity, colon cancer, inflammatory bowel disease, inflammaging and neurodegeneration. Fortunately, a probiotic regime with a diet rich in prebiotics may reverse dysbiosis promoting health and wellness in age. The current study designs, optimizes and tests a novel probiotic and synbiotic formulation consisting of three metabolically active probiotics Lactobacillus plantarum, Lactobacillus fermentum and Bifidobacteria infantis together with a novel polyphenol-rich prebiotic, Triphala...
April 12, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29615570/drosophila-as-a-model-to-study-the-link-between-metabolism-and-cancer
#5
REVIEW
Héctor Herranz, Stephen M Cohen
Cellular metabolism has recently been recognized as a hallmark of cancer. Investigating the origin and effects of the reprogrammed metabolism of tumor cells, and identifying its genetic mediators, will improve our understanding of how these changes contribute to disease progression and may suggest new approaches to therapy. Drosophila melanogaster is emerging as a valuable model to study multiple aspects of tumor formation and malignant transformation. In this review, we discuss the use of Drosophila as model to study how changes in cellular metabolism, as well as metabolic disease, contribute to cancer...
December 1, 2017: Journal of Developmental Biology
https://www.readbyqxmd.com/read/29615557/wingless-wnt-signaling-in-intestinal-development-homeostasis-regeneration-and-tumorigenesis-a-drosophila-perspective
#6
REVIEW
Ai Tian, Hassina Benchabane, Yashi Ahmed
In mammals, the Wnt/β-catenin signal transduction pathway regulates intestinal stem cell maintenance and proliferation, whereas Wnt pathway hyperactivation, resulting primarily from the inactivation of the tumor suppressor Adenomatous polyposis coli (APC), triggers the development of the vast majority of colorectal cancers. The Drosophila adult gut has recently emerged as a powerful model to elucidate the mechanisms by which Wingless/Wnt signaling regulates intestinal development, homeostasis, regeneration, and tumorigenesis...
March 28, 2018: Journal of Developmental Biology
https://www.readbyqxmd.com/read/29615551/the-biology-of-sumo-targeted-ubiquitin-ligases-in-drosophila-development-immunity-and-cancer
#7
REVIEW
Mona Abed, Eliya Bitman-Lotan, Amir Orian
The ubiquitin and SUMO (small ubiquitin-like modifier) pathways modify proteins that in turn regulate diverse cellular processes, embryonic development, and adult tissue physiology. These pathways were originally discovered biochemically in vitro, leading to a long-standing challenge of elucidating both the molecular cross-talk between these pathways and their biological importance. Recent discoveries in Drosophila established that ubiquitin and SUMO pathways are interconnected via evolutionally conserved SUMO-targeted ubiquitin ligase (STUbL) proteins...
January 1, 2018: Journal of Developmental Biology
https://www.readbyqxmd.com/read/29602952/regulation-of-the-hippo-pathway-in-cancer-biology
#8
REVIEW
Sungho Moon, So Yeon Park, Hyun Woo Park
The Hippo tumor suppressor pathway, which is well conserved from Drosophila to humans, has emerged as the master regulator of organ size, as well as major cellular properties, such as cell proliferation, survival, stemness, and tissue homeostasis. The biological significance and deregulation of the Hippo pathway in tumorigenesis have received a surge of interest in the past decade. In the current review, we present the major discoveries that made substantial contributions to our understanding of the Hippo pathway and discuss how Hippo pathway components contribute to cellular signaling, physiology, and their potential implications in anticancer therapeutics...
March 30, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29602250/the-role-of-septin-7-in-physiology-and-pathological-disease-a-systematic-review-of-current-status
#9
REVIEW
Xinlu Wang, Fei Fei, Jie Qu, Chunyuan Li, Yuwei Li, Shiwu Zhang
Septins are a conserved family of cytoskeletal GTPases present in different organisms, including yeast, drosophila, Caenorhabditis elegans and humans. In humans, septins are involved in various cellular processes, including exocytosis, apoptosis, leukemogenesis, carcinogenesis and neurodegeneration. Septin 7 is unique out of 13 human septins. Mammalian septin 6, septin 7, septin 2 and septin 9 coisolate together in complexes to form the core unit for the generation of the septin filaments. Physiological septin filaments are hetero-oligomeric complexes consisting of core septin hexamers and octamers...
March 30, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29578365/the-capicua-tumor-suppressor-a-gatekeeper-of-ras-signaling-in-development-and-cancer
#10
Lucía Simón-Carrasco, Gerardo Jiménez, Mariano Barbacid, Matthias Drosten
The transcriptional repressor Capicua (CIC) has emerged as an important rheostat of cell growth regulated by RAS/MAPK signaling. Cic was originally discovered in Drosophila, where it was shown to be inactivated by MAPK signaling downstream of the RTKs Torso and EGFR, which results in signal-dependent responses that are required for normal cell fate specification, proliferation and survival of developing and adult tissues. CIC is highly conserved in mammals, where it is also negatively regulated by MAPK signaling...
March 26, 2018: Cell Cycle
https://www.readbyqxmd.com/read/29560857/a-switch-in-transcription-and-cell-fate-governs-the-onset-of-an-epigenetically-deregulated-tumor-in-drosophila
#11
Joana Torres, Remo Monti, Ariane L Moore, Makiko Seimiya, Yanrui Jiang, Niko Beerenwinkel, Christian Beisel, Jorge V Beira, Renato Paro
Tumor initiation is often linked to a loss of cellular identity. Transcriptional programs determining cellular identity are preserved by epigenetically-acting chromatin factors. Although such regulators are among the most frequently mutated genes in cancer, it is not well understood how an abnormal epigenetic condition contributes to tumor onset. In this work, we investigated the gene signature of tumors caused by disruption of the Drosophila epigenetic regulator, polyhomeotic (ph). In larval tissue ph mutant cells show a shift towards an embryonic-like signature...
March 21, 2018: ELife
https://www.readbyqxmd.com/read/29555768/division-independent-differentiation-mandates-proliferative-competition-among-stem-cells
#12
Amy Reilein, David Melamed, Simon Tavaré, Daniel Kalderon
Cancer-initiating gatekeeper mutations that arise in stem cells would be especially potent if they stabilize and expand an affected stem cell lineage. It is therefore important to understand how different stem cell organization strategies promote or prevent variant stem cell amplification in response to different types of mutation, including those that activate proliferation. Stem cell numbers can be maintained constant while producing differentiated products through individually asymmetrical division outcomes or by population asymmetry strategies in which individual stem cell lineages necessarily compete for niche space...
March 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29547901/molecular-partners-of-hnot-alg3-the-human-counterpart-of-the-drosophila-not-and-yeast-alg3-gene-suggest-its-involvement-in-distinct-cellular-processes-relevant-to-congenital-disorders-of-glycosylation-cancer-neurodegeneration-and-a-variety-of-further-pathologies
#13
Benedikt Hacker, Christoph Schultheiß, Michael Döring, Ursula Kurzik-Dumke
This study provides first insights into the involvement of hNOT/ALG3, the human counterpart of the Drosophila NOT and yeast ALG3 gene, in various putative molecular networks. HNOT/ALG3 encodes two translated transcripts encoding precursor proteins differing in their N-terminus and showing 33% identity with the yeast asparagine-linked glycosylation 3 (ALG3) protein. Experimental evidence for the functional homology of the proteins of fly and man in the N-glycosylation has still to be provided. In this study, using the yeast two-hybrid technique we identify 17 molecular partners of hNOT-1/ALG3-1...
March 14, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29546880/cell-motility-in-cancer-invasion-and-metastasis-insights-from-simple-model-organisms
#14
REVIEW
Christina H Stuelten, Carole A Parent, Denise J Montell
Metastasis remains the greatest challenge in the clinical management of cancer. Cell motility is a fundamental and ancient cellular behaviour that contributes to metastasis and is conserved in simple organisms. In this Review, we evaluate insights relevant to human cancer that are derived from the study of cell motility in non-mammalian model organisms. Dictyostelium discoideum, Caenorhabditis elegans, Drosophila melanogaster and Danio rerio permit direct observation of cells moving in complex native environments and lend themselves to large-scale genetic and pharmacological screening...
March 16, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29545526/functional-analysis-of-the-drosophila-rhogap-cv-c-protein-and-its-equivalence-to-the-human-dlc3-and-dlc1-proteins
#15
Sol Sotillos, Mario Aguilar-Aragon, James Castelli-Gair Hombría
RhoGAP proteins control the precise regulation of the ubiquitous small RhoGTPases. The Drosophila Crossveinless-c (Cv-c) RhoGAP is homologous to the human tumour suppressor proteins Deleted in Liver Cancer 1-3 (DLC1-3) sharing an identical arrangement of SAM, GAP and START protein domains. Here we analyse in Drosophila the requirement of each Cv-c domain to its function and cellular localization. We show that the basolateral membrane association of Cv-c is key for its epithelial function and find that the GAP domain targeted to the membrane can perform its RhoGAP activity independently of the rest of the protein, implying the SAM and START domains perform regulatory roles...
March 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29542037/autophagy-stimulation-as-a-promising-approach-in-treatment-of-neurodegenerative-diseases
#16
REVIEW
Karolina Pierzynowska, Lidia Gaffke, Zuzanna Cyske, Michał Puchalski, Estera Rintz, Michał Bartkowski, Marta Osiadły, Michał Pierzynowski, Jagoda Mantej, Ewa Piotrowska, Grzegorz Węgrzyn
Autophagy is a process of degradation of macromolecules in the cytoplasm, particularly proteins of a long half-life, as well as whole organelles, in eukaryotic cells. Lysosomes play crucial roles during this degradation. Autophagy is a phylogenetically old, and evolutionarily conserved phenomenon which occurs in all eukaryotic cells. It can be found in yeast Saccharomyces cerevisiae, insect Drosophila melanogaster, and mammals, including humans. Its high importance for cell physiology has been recognized, and in fact, dysfunctions causing impaired autophagy are associated with many severe disorders, including cancer and metabolic brain diseases...
March 14, 2018: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29535423/jnk-and-yorkie-drive-tumor-progression-by-generating-polyploid-giant-cells-in-drosophila
#17
Bojie Cong, Shizue Ohsawa, Tatsushi Igaki
Epithelial cancer tissues often possess polyploid giant cells, which are thought to be highly oncogenic. However, the mechanisms by which polyploid giant cells are generated in tumor tissues and how such cells contribute to tumor progression remain elusive. We previously noticed in Drosophila imaginal epithelium that cells mutant for the endocytic gene rab5 exhibit enlarged nuclei. Here we find that mutations in endocytic 'neoplastic tumor-suppressor' genes, such as rab5, vps25, erupted, or avalanche result in generation of polyploid giant cells...
March 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29533772/apc-inhibits-ligand-independent-wnt-signaling-by-the-clathrin-endocytic-pathway
#18
Kenyi Saito-Diaz, Hassina Benchabane, Ajit Tiwari, Ai Tian, Bin Li, Joshua J Thompson, Annastasia S Hyde, Leah M Sawyer, Jeanne N Jodoin, Eduardo Santos, Laura A Lee, Robert J Coffey, R Daniel Beauchamp, Christopher S Williams, Anne K Kenworthy, David J Robbins, Yashi Ahmed, Ethan Lee
Adenomatous polyposis coli (APC) mutations cause Wnt pathway activation in human cancers. Current models for APC action emphasize its role in promoting β-catenin degradation downstream of Wnt receptors. Unexpectedly, we find that blocking Wnt receptor activity in APC-deficient cells inhibits Wnt signaling independently of Wnt ligand. We also show that inducible loss of APC is rapidly followed by Wnt receptor activation and increased β-catenin levels. In contrast, APC2 loss does not promote receptor activation...
March 12, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29514083/pi3k-akt-cooperates-with-oncogenic-notch-by-inducing-nitric-oxide-dependent-inflammation
#19
Santiago Nahuel Villegas, Rita Gombos, Lucia García-López, Irene Gutiérrez-Pérez, Jesús García-Castillo, Diana Marcela Vallejo, Vanina Gabriela Da Ros, Esther Ballesta-Illán, József Mihály, Maria Dominguez
The PI3K/Akt signaling pathway, Notch, and other oncogenes cooperate in the induction of aggressive cancers. Elucidating how the PI3K/Akt pathway facilitates tumorigenesis by other oncogenes may offer opportunities to develop drugs with fewer side effects than those currently available. Here, using an unbiased in vivo chemical genetic screen in Drosophila, we identified compounds that inhibit the activity of proinflammatory enzymes nitric oxide synthase (NOS) and lipoxygenase (LOX) as selective suppressors of Notch-PI3K/Akt cooperative oncogenesis...
March 6, 2018: Cell Reports
https://www.readbyqxmd.com/read/29498662/wnt-signalling-in-intestinal-stem-cells-lessons-from-mice-and-flies
#20
REVIEW
Jessica Perochon, Lynsey R Carroll, Julia B Cordero
Adult stem cells play critical roles in the basal maintenance of tissue integrity, also known as homeostasis, and in tissue regeneration following damage. The highly conserved Wnt signalling pathway is a key regulator of stem cell fate. In the gastrointestinal tract, Wnt signalling activation drives homeostasis and damage-induced repair. Additionally, deregulated Wnt signalling is a common hallmark of age-associated tissue dysfunction and cancer. Studies using mouse and fruit fly models have greatly improved our understanding of the functional contribution of the Wnt signalling pathway in adult intestinal biology...
March 2, 2018: Genes
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