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https://www.readbyqxmd.com/read/27899382/a-metastatic-mouse-model-identifies-genes-that-regulate-neuroblastoma-metastasis
#1
Bo Kyung Alex Seong, Kelly E Fathers, Robin M Hallett, Christina K Yung, Lincoln D Stein, Samar Mouaaz, Lynn Kee, Cynthia Hawkins, Meredith S Irwin, David R Kaplan
Metastatic relapse is the major cause of death in pediatric neuroblastoma (NB), where there remains a lack of therapies to target this stage of disease. To understand the molecular mechanisms mediating NB metastasis, we developed a mouse model using intracardiac injection and in vivo selection to isolate malignant cell subpopulations with a higher propensity for metastasis to bone and the central nervous system. Gene expression profiling revealed primary and metastatic cells as two distinct cell populations defined by differential expression 412 genes and multiple pathways, including CADM1, SPHK1 and YAP/TAZ whose expression independently predicted survival...
November 29, 2016: Cancer Research
https://www.readbyqxmd.com/read/27885187/-role-of-hippo-yap-taz-signaling-pathway-in-mechanotransduction
#2
Erika Ishihara, Hiroshi Nishina
Transcriptional coactivators YAP(yes associated protein)and TAZ(transcriptional coactivator with PDZ-binding motif)regulate gene expression through binding to transcription factors. Recently, some studies showed that YAP/TAZ activity responded to mechanical inputs such as stiffness of the extracellular matrix and the mechanical regulation of YAP/TAZ controlled cell proliferation or differentiation. Additionally, we revealed important roles of YAP in tissue formation and homeostasis through cellular tension and pressure...
2016: Clinical Calcium
https://www.readbyqxmd.com/read/27881410/taz-activation-drives-fibroblast-spheroid-growth-expression-of-pro-fibrotic-paracrine-signals-and-context-dependent-ecm-gene-expression
#3
Amy J Jorgenson, Kyoung Moo Choi, Delphine Sicard, Karry M J Smith, Samantha E Hiemer, Xaralabos Varelas, Daniel J Tschumperlin
Recent studies have implicated the Hippo pathway and its transcriptional effectors YAP and TAZ as necessary for fibroblast activation and tissue fibrosis. To test the specific and sufficient roles for TAZ in driving autonomous fibroblast activation, we cultured NIH3T3 fibroblasts expressing a doxycycline-inducible nuclear-localized mutant of TAZ (TAZ4SA) in scaffold-free 3D hanging drop spheroids, or on matrices of specified mechanical rigidity. Control NIH3T3 fibroblasts formed spheroids in hanging drop culture that remained stable and neither increased nor decreased in size significantly over 15 days...
November 23, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27881216/interacting-network-of-hippo-wnt-%C3%AE-catenin-and-notch-signaling-represses-liver-tumor-formation
#4
Wantae Kim, Sanjoy Kumar Khan, Yingzi Yang
Acquiring a selective growth advantage by breaking the proliferation barrier established by gatekeeper genes is a centrally important event in tumor formation. Removal of mammalian Hippo kinase Mst1 and Mst2 in hepatocytes leads to very rapid hepatocellular carcinoma (HCC) formation, indicating that the Hippo signaling pathway is a critical gatekeeper in hepatocytes that restrains abnormal growth. By rigorous genetic approaches, we have identified an interacting network of the Hippo, Wnt/β-catenin and Notch signaling pathways that controls organ size and HCC development...
November 24, 2016: BMB Reports
https://www.readbyqxmd.com/read/27874005/the-hippo-signalling-pathway-coordinates-organ-growth-and-limits-developmental-variability-by-controlling-dilp8-expression
#5
Emilie Boone, Julien Colombani, Ditte S Andersen, Pierre Léopold
Coordination of organ growth during development is required to generate fit individuals with fixed proportions. We recently identified Drosophila Dilp8 as a key hormone in coupling organ growth with animal maturation. In addition, dilp8 mutant flies exhibit elevated fluctuating asymmetry (FA) demonstrating a function for Dilp8 in ensuring developmental stability. The signals regulating Dilp8 activity during normal development are not yet known. Here, we show that the transcriptional co-activators of the Hippo (Hpo) pathway, Yorkie (Yki, YAP/TAZ) and its DNA-binding partner Scalloped (Sd), directly regulate dilp8 expression through a Hpo-responsive element (HRE) in the dilp8 promoter...
November 22, 2016: Nature Communications
https://www.readbyqxmd.com/read/27873451/a-prospective-randomized-trial-comparing-piperacillin-tazobactam-with-meropenem-as-empirical-antibiotic-treatment-of-febrile-neutropenic-children-and-adolescents-with-hematologic-and-malignant-disorders
#6
Hirozumi Sano, Ryoji Kobayashi, Daisuke Suzuki, Daiki Hori, Kenji Kishimoto, Kunihiko Kobayashi
BACKGROUND: This randomized prospective study was designed to assess whether piperacillin/tazobactam (PIPC/TAZ) is as effective as meropenem (MEPM) as a first-line antibiotic treatment for febrile neutropenia (FN). PROCEDURE: FN episodes were randomly assigned to receive either PIPC/TAZ (337.5 mg/kg per day in three doses, 1-hr DIV, maximum 13.5 g per day) or MEPM (120 mg/kg per day in three doses, 1-hr DIV, maximum 3 g per day). Clinical responses were evaluated 120 hr after the DIV...
November 22, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27872080/classical-%C3%AE-lactamase-inhibitors-potentiate-the-activity-of-daptomycin-against-methicillin-resistant-staphylococcus-aureus-and-colistin-against-acinetobacter-baumannii
#7
George Sakoulas, Warren Rose, Andrew Berti, Joshua Olson, Jason Mungia, Poochit Nonejuie, Eleanna Sakoulas, Michael J Rybak, Joseph Pogliano, Victor Nizet
We asked whether beta-lactamase inhibitors (BLIs) increased the activity of daptomycin (DAP) against methicillin-resistant Staphylococcus aureus (MRSA), peptide antibiotic colistin (COL) against emerging Gram-negative nosocomial pathogen Acinetobacter baumannii, and human host defense peptide cathelicidin LL37 against either pathogen. DAP and LL37 kill curves were performed with or without BLIs against MRSA, vancomycin-intermediate S. aureus (VISA) and heterogeneous-VISA (hVISA). COL and LL37 kill curves were performed against A...
November 21, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27869648/hippo-signaling-interactions-with-wnt-%C3%AE-catenin-and-notch-signaling-repress-liver-tumorigenesis
#8
Wantae Kim, Sanjoy Kumar Khan, Jelena Gvozdenovic-Jeremic, Youngeun Kim, Jason Dahlman, Hanjun Kim, Ogyi Park, Tohru Ishitani, Eek-Hoon Jho, Bin Gao, Yingzi Yang
Malignant tumors develop through multiple steps of initiation and progression, and tumor initiation is of singular importance in tumor prevention, diagnosis, and treatment. However, the molecular mechanism whereby a signaling network of interacting pathways restrains proliferation in normal cells and prevents tumor initiation is still poorly understood. Here, we have reported that the Hippo, Wnt/β-catenin, and Notch pathways form an interacting network to maintain liver size and suppress hepatocellular carcinoma (HCC)...
November 21, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27853118/traditional-living-habits-of-the-taz-tundra-population-a-paleoparasitological-study
#9
Sergey Mikhailovich Slepchenko, Sergey Nikolaevich Ivanov, Bagashev Anatoly Nikolaevich, Tsybankov Alexander Alekseevich, Slavinsky Vyacheslav Sergeyevich
An excavation of the Vesakoyakha II-IV and Nyamboyto I burial grounds was conducted during the 2014 field season, and soil samples from intact burials dating from the 19th and 20th centuries, respectively, were analyzed to determine interactions between parasites and host/vectors. Considering the discovery of Diphyllobothrium sp. and Taenia sp. eggs in soil samples from the pelvic region, diphyllobothriasis was the most frequent helminthic infection among the Taz Nenets. The Nyamboyto Nenets mainly consumed uncooked fish, while the Vesakoyakha Nenets had a bigger variety in food choices, including reindeer meat...
October 2016: Korean Journal of Parasitology
https://www.readbyqxmd.com/read/27852064/overexpression-of-fzd7-promotes-glioma-cell-proliferation-by-upregulating-taz
#10
Xia Qiu, Jianguo Jiao, Yidong Li, Tian Tian
Gliomas are the most prevalent type of primary brain tumors in adults, accounting for more than 40% of neoplasm in the central nervous system. Frizzled-7 (FZD7) is a seven-pass trans-membrane Wnt receptor that plays a critical role in the development of various tumors. In this study, we detected high-level FZD7 expression in glioma and its overexpression was associated with advanced tumor stage. In vitro functional assays showed that forced overexpression of FZD7 promoted proliferation of gliomas cells, whereas knockdown of endogenous FZD7 significantly suppressed proliferation ability of these cells...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27851961/wip-drives-tumor-progression-through-yap-taz-dependent-autonomous-cell-growth
#11
Ricardo Gargini, Maribel Escoll, Esther García, Ramón García-Escudero, Francisco Wandosell, Inés María Antón
In cancer, the deregulation of growth signaling pathways drives changes in the cell's architecture and its environment that allow autonomous growth of tumors. These cells then acquire a tumor-initiating "stemness" phenotype responsible for disease advancement to more aggressive stages. Here, we show that high levels of the actin cytoskeleton-associated protein WIP (WASP-interacting protein) correlates with tumor growth, both of which are linked to the tumor-initiating cell phenotype. We find that WIP controls tumor growth by boosting signals that stabilize the YAP/TAZ complex via a mechanism mediated by the endocytic/endosomal system...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27847303/sumoylation-of-large-tumor-suppressor-1-at-lys751-attenuates-its-kinase-activity-and-tumor-suppressor-functions
#12
Liu Mei, Lianwen Yuan, Wei Shi, Shihao Fan, Chao Tang, Xueying Fan, Wanlei Yang, Yu Qian, Musaddique Hussain, Ximei Wu
Large tumor suppressor (Lats) plays a critical role in maintaining cellular homeostasis and is the core to mediate Hippo growth-inhibitory signaling pathway. SUMOylation is a reversible and dynamic process that regulates a variety of cell functions. Here, we show that SUMOylation of Lats1 affects its kinase activity specifically towards Hippo signaling. Small ubiquitin-like modifier (SUMO) 1 interacts with and directly SUMOylates Lats1, whereas loss of SUMOylation pathway function disrupts Lats1 SUMOylation...
November 12, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27829622/morphological-and-mechanical-properties-of-osteosarcoma-microenvironment-cells-explored-by-atomic-force-microscopy
#13
Xinlong Wang, Yingjun Yang, Xiaohong Hu, Naoki Kawazoe, Yingnan Yang, Guoping Chen
Cell mechanical properties that depend on cytoskeleton architecture are critical to the mechanotransduction process, and have great potential for cancer diagnosis and therapy. In this study, the morphological and mechanical properties of typical osteosarcoma microenvironment cells, including mesenchymal stem cells (MSC), normal human osteoblast cells (NHOst) and osteosarcoma cells (MG-63), were compared using atomic force microscopy (AFM). The MG-63 cells were smaller and thicker than the MSC and NHOst cells...
2016: Analytical Sciences: the International Journal of the Japan Society for Analytical Chemistry
https://www.readbyqxmd.com/read/27829313/taz-induction-directs-differentiation-of-thyroid-follicular-cells-from-human-embryonic-stem-cells
#14
Risheng Ma, Syed Morshed, Rauf Latif, Terry F Davies
OBJECTIVE: The differentiation program for human thyroid follicular cells (TFCs) relies on the interplay between sequence-specific transcription factors and transcriptional co-regulators. TAZ (transcriptional co-activator with PDZ-binding motif) is a co-activator that regulates several transcription factors, including PAX8 and NKX2-1, which play a central role in thyroid-specific gene transcription. TAZ and PAX8/NKX2-1 are co-expressed in the nuclei of thyroid cells and TAZ interacts directly with both PAX8 and NKX2-1 leading to their enhanced transcriptional activity on the thyroglobulin (TG) promoter and additional genes...
November 9, 2016: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/27826870/hippo-signaling-in-mitosis-an-updated-view-in-light-of-the-men-pathway
#15
Alexander Hergovich
The Hippo pathway is an essential tumor suppressor signaling network that coordinates cell proliferation, death, and differentiation in higher eukaryotes. Intriguingly, the core components of the Hippo pathway are conserved from yeast to man, with the yeast analogs of mammalian MST1/2 (fly Hippo), MOB1 (fly Mats), LATS1/2 (fly Warts), and NDR1/2 (fly Tricornered) functioning as essential components of the mitotic exit network (MEN). Here, we update our previous summary of mitotic functions of Hippo core components in Drosophila melanogaster and mammals, with particular emphasis on similarities between the yeast MEN pathway and mitotic Hippo signaling...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27826640/role-of-yap-taz-transcriptional-regulators-in-resistance-to-anti-cancer-therapies
#16
REVIEW
Min Hwan Kim, Joon Kim
A diverse range of drug resistance mechanisms in cancer cells and their microenvironment significantly reduces the effectiveness of anti-cancer therapies. Growing evidence suggests that transcriptional effectors of the Hippo pathway, YAP and TAZ, promote resistance to various anti-cancer therapies, including cytotoxic chemotherapy, molecular targeted therapy, and radiation therapy. Here, we overview the role of YAP and TAZ as drug resistance mediators, and also discuss potential upstream regulators and downstream targets of YAP/TAZ in cancer...
November 8, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27815996/human-airway-organoid-engineering-as-a-step-toward-lung-regeneration-and-disease-modeling
#17
Qi Tan, Kyoung Moo Choi, Delphine Sicard, Daniel J Tschumperlin
Organoids represent both a potentially powerful tool for the study cell-cell interactions within tissue-like environments, and a platform for tissue regenerative approaches. The development of lung tissue-like organoids from human adult-derived cells has not previously been reported. Here we combined human adult primary bronchial epithelial cells, lung fibroblasts, and lung microvascular endothelial cells in supportive 3D culture conditions to generate airway organoids. We demonstrate that randomly-seeded mixed cell populations undergo rapid condensation and self-organization into discrete epithelial and endothelial structures that are mechanically robust and stable during long term culture...
October 28, 2016: Biomaterials
https://www.readbyqxmd.com/read/27797825/mcm7-and-its-hosted-mir-25-93-and-106b-cluster-elicit-yap-taz-oncogenic-activity-in-lung-cancer
#18
F Lo Sardo, M Forcato, A Sacconi, V Capaci, F Zanconato, S di Agostino, G Del Sal, P P Pandolfi, S Strano, S Bicciato, G Blandino
Lung cancer is the first cause of cancer death worldwide and the Hippo pathway transcriptional coactivators YAP/TAZ have a pro-oncogenic role in this context. In order to understand the mechanisms through which YAP/TAZ elicit their oncogenic role in different systems, many studies are focused on YAP/TAZ target genes involved in the regulation of cell proliferation/survival and migration. However, there is scarce evidence on the role of YAP/TAZ in microRNA regulation while there is increasing evidence supporting the role of microRNAs in the main oncogenic processes...
October 17, 2016: Carcinogenesis
https://www.readbyqxmd.com/read/27797343/reciprocal-stabilization-of-abl-and-taz-regulates-osteoblastogenesis-through-transcription-factor-runx2
#19
Yoshinori Matsumoto, Jose La Rose, Oliver A Kent, Melany J Wagner, Masahiro Narimatsu, Aaron D Levy, Mitchell H Omar, Jiefei Tong, Jonathan R Krieger, Emily Riggs, Yaryna Storozhuk, Julia Pasquale, Manuela Ventura, Behzad Yeganeh, Martin Post, Michael F Moran, Marc D Grynpas, Jeffrey L Wrana, Giulio Superti-Furga, Anthony J Koleske, Ann Marie Pendergast, Robert Rottapel
Cellular identity in metazoan organisms is frequently established through lineage-specifying transcription factors, which control their own expression through transcriptional positive feedback, while antagonizing the developmental networks of competing lineages. Here, we have uncovered a distinct positive feedback loop that arises from the reciprocal stabilization of the tyrosine kinase ABL and the transcriptional coactivator TAZ. Moreover, we determined that this loop is required for osteoblast differentiation and embryonic skeletal formation...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27770688/the-effect-of-zonal-factors-in-estimating-crash-risks-by-transportation-modes-motor-vehicle-bicycle-and-pedestrian
#20
Jie Wang, Helai Huang, Qiang Zeng
OBJECTIVES: This paper aimed to (i) differentiate the effects of contributory factors on crash risks related to different transportation modes, i.e., motor vehicle, bicycle and pedestrian; (ii) explore the potential contribution of zone-level factors which are traditionally excluded or omitted, so as to track the source of heterogeneous effects of certain risk factors in crash-frequency models by different modes. METHODS: Two analytical methods, i.e. negative binomial models (NB) and random parameters negative binomial models (RPNB), were employed to relate crash frequencies of different transportation modes to a variety of risk factors at intersections...
October 19, 2016: Accident; Analysis and Prevention
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