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https://www.readbyqxmd.com/read/28098159/fluid-shear-stress-activates-yap1-to-promote-cancer-cell-motility
#1
Hyun Jung Lee, Miguel F Diaz, Katherine M Price, Joyce A Ozuna, Songlin Zhang, Eva M Sevick-Muraca, John P Hagan, Pamela L Wenzel
Mechanical stress is pervasive in egress routes of malignancy, yet the intrinsic effects of force on tumour cells remain poorly understood. Here, we demonstrate that frictional force characteristic of flow in the lymphatics stimulates YAP1 to drive cancer cell migration; whereas intensities of fluid wall shear stress (WSS) typical of venous or arterial flow inhibit taxis. YAP1, but not TAZ, is strictly required for WSS-enhanced cell movement, as blockade of YAP1, TEAD1-4 or the YAP1-TEAD interaction reduces cellular velocity to levels observed without flow...
January 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28087714/dlg5-connects-cell-polarity-and-hippo-signaling-protein-networks-by-linking-par-1-with-mst1-2
#2
Julian Kwan, Anna Sczaniecka, Emad Heidary Arash, Liem Nguyen, Chia-Chun Chen, Srdjana Ratkovic, Olga Klezovitch, Liliana Attisano, Helen McNeill, Andrew Emili, Valeri Vasioukhin
Disruption of apical-basal polarity is implicated in developmental disorders and cancer; however, the mechanisms connecting cell polarity proteins with intracellular signaling pathways are largely unknown. We determined previously that membrane-associated guanylate kinase (MAGUK) protein discs large homolog 5 (DLG5) functions in cell polarity and regulates cellular proliferation and differentiation via undefined mechanisms. We report here that DLG5 functions as an evolutionarily conserved scaffold and negative regulator of Hippo signaling, which controls organ size through the modulation of cell proliferation and differentiation...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28078823/hippo-vs-crab-tissue-specific-functions-of-the-mammalian-hippo-pathway
#3
REVIEW
Miki Nishio, Tomohiko Maehama, Hiroki Goto, Keisuke Nakatani, Wakako Kato, Hirofumi Omori, Yosuke Miyachi, Hideru Togashi, Yohei Shimono, Akira Suzuki
The Hippo signaling pathway is a vital suppressor of tumorigenesis that is often inactivated in human cancers. In normal cells, the Hippo pathway is triggered by external forces such as cell crowding, or changes to the extracellular matrix or cell polarity. Once activated, Hippo signaling down-regulates transcription supported by the paralogous cofactors YAP1 and TAZ. The Hippo pathway's functions in normal and cancer biology have been dissected by studies of mutant mice with null or conditional tissue-specific mutations of Hippo signaling elements...
January 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28070695/barth-syndrome-connecting-cardiolipin-to-cardiomyopathy
#4
REVIEW
Nikita Ikon, Robert O Ryan
The Barth syndrome (BTHS) is caused by an inborn error of metabolism that manifests characteristic phenotypic features including altered mitochondrial membrane phospholipids, lactic acidosis, organic acid-uria, skeletal muscle weakness and cardiomyopathy. The underlying cause of BTHS has been definitively traced to mutations in the tafazzin (TAZ) gene locus on chromosome X. TAZ encodes a phospholipid transacylase that promotes cardiolipin acyl chain remodeling. Absence of tafazzin activity results in cardiolipin molecular species heterogeneity, increased levels of monolysocardiolipin and lower cardiolipin abundance...
January 9, 2017: Lipids
https://www.readbyqxmd.com/read/28068668/the-hippo-kinases-lats1-and-2-control-human-breast-cell-fate-via-crosstalk-with-er%C3%AE
#5
Adrian Britschgi, Stephan Duss, Sungeun Kim, Joana Pinto Couto, Heike Brinkhaus, Shany Koren, Duvini De Silva, Kirsten D Mertz, Daniela Kaup, Zsuzsanna Varga, Hans Voshol, Alexandra Vissieres, Cedric Leroy, Tim Roloff, Michael B Stadler, Christina H Scheel, Loren J Miraglia, Anthony P Orth, Ghislain M C Bonamy, Venkateshwar A Reddy, Mohamed Bentires-Alj
Cell fate perturbations underlie many human diseases, including breast cancer. Unfortunately, the mechanisms by which breast cell fate are regulated are largely unknown. The mammary gland epithelium consists of differentiated luminal epithelial and basal myoepithelial cells, as well as undifferentiated stem cells and more restricted progenitors. Breast cancer originates from this epithelium, but the molecular mechanisms that underlie breast epithelial hierarchy remain ill-defined. Here, we use a high-content confocal image-based short hairpin RNA screen to identify tumour suppressors that regulate breast cell fate in primary human breast epithelial cells...
January 9, 2017: Nature
https://www.readbyqxmd.com/read/28068223/hepatocyte-taz-wwtr1-promotes-inflammation-and-fibrosis-in-nonalcoholic-steatohepatitis
#6
Xiaobo Wang, Ze Zheng, Jorge Matias Caviglia, Kathleen E Corey, Tina M Herfel, Bishuang Cai, Ricard Masia, Raymond T Chung, Jay H Lefkowitch, Robert F Schwabe, Ira Tabas
Nonalcoholic steatohepatitis (NASH) is a leading cause of liver disease worldwide. However, the molecular basis of how benign steatosis progresses to NASH is incompletely understood, which has limited the identification of therapeutic targets. Here we show that the transcription regulator TAZ (WWTR1) is markedly higher in hepatocytes in human and murine NASH liver than in normal or steatotic liver. Most importantly, silencing of hepatocyte TAZ in murine models of NASH prevented or reversed hepatic inflammation, hepatocyte death, and fibrosis, but not steatosis...
December 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28068221/devilish-effects-of-taz-in-nonalcoholic-steatohepatitis
#7
Scott L Friedman, Youngmin A Lee
Nonalcoholic steatohepatitis leads to cirrhosis and cancer in a rising number of patients with metabolic syndrome. In this issue of Cell Metabolism, Wang et al. (2016) identify the transcriptional co-activator Taz as a driver of inflammation and fibrosis through the induction of Indian hedgehog in hepatocytes, which stimulates fibrogenesis by hepatic stellate cells.
December 13, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28061504/dub3-deubiquitylating-enzymes-regulate-hippo-pathway-activity-by-regulating-the-stability-of-itch-lats-and-amot-proteins
#8
Hung Thanh Nguyen, Jan-Michael Kugler, Stephen M Cohen
The YAP and TAZ transcriptional coactivators promote oncogenic transformation. Elevated YAP/TAZ activity has been documented in human tumors. YAP and TAZ are negatively regulated by the Hippo tumor suppressor pathway. The activity and stability of several Hippo pathway components, including YAP/TAZ, is regulated by ubiquitin mediated protein turnover and several ubiquitin ligase complexes have been implicated in human cancer. However, little is known about the deubiquitylating enzymes that counteract these ubiquitin ligases in regulation of the Hippo pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28058603/communities-of-bacteria-and-viruses-in-waters-of-the-gulf-of-ob-and-taz-estuary
#9
M A Pavlova, P R Makarevich, T I Shirokolobova
The study of the most abundant components in freshwater plankton in the Gulf of Ob and Taz Estuary in the summer-autumn season has demonstrated that the abundance and biomass of bacteria are stable and typical for mesotrophic waters during active microalgae vegetation. The abundance of viral particles varies in the range which is reported for unproductive or medium-productive water bodies. The environmental factors affecting affect the development and patterns of bacterio- and virioplankton distribution are considered...
November 2016: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/28055015/the-taz-mir-224-smad4-axis-promotes-tumorigenesis-in-osteosarcoma
#10
Jianjun Ma, Kangmao Huang, Yan Ma, Menglu Zhou, Shunwu Fan
Transcriptional co-activator with PDZ-binding motif (TAZ) is a downstream effector of the Hippo signaling pathway that participates in tumorigenesis. The aim of this study was to identify the miRNA counterpart for TAZ and elucidate the mechanism underlying the tumorigenic effect of TAZ. We demonstrated that TAZ is upregulated in osteosarcoma (OS) tissues and cell lines, and that TAZ overexpression can induce cell migration, invasion and proliferation. Moreover, miRNA-224 (miR-224), a TAZ phenocopy that functions downstream of TAZ, was found to be upregulated with TAZ overexpression...
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28052865/keeping-fibroblasts-in-suspense-taz-mediated-signaling-activates-a-context-dependent-pro-fibrotic-phenotype
#11
Bram Piersma, Ruud A Bank
N/A.
January 4, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28048702/tu-h-brc-01-a-new-fabrication-method-for-secondary-skin-collimation-using-3d-scanner-and-3d-printer
#12
J Jung, N Potter, T Suh, C Liu, B Lu
PURPOSE: Using secondary skin collimation (SSC) to protect the critical organ surrounding the tumors is always desirable for electron and/or ortho-voltage treatments. However, the time-consuming and labor-intensive fabrication processes of current method (manually fabricate the lead mask) restrict the general use of SSC. The aim of this study is to develop a new SSC fabrication method using 3D scanning and 3D printing technologies in order to largely decrease the human labor involvement and fabrication time, also improve the fabrication accuracy...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28045538/micropore-formation-of-zn2-oxac-taz-2-%C3%A2-h2o-2-5-via-co2-adsorption
#13
Moondra Zubir, Atom Hamasaki, Taku Iiyama, Akira Ohta, Hiroshi Ohki, Sumio Ozeki
As-synthesized [Zn2(Oxac)(Taz)2]•(H2O)2.5, referred to ZOTW2.5, was prepared from aqueous methanol solutions of Zn5(CO3)2(OH)6 and two kinds of ligands of 1,2,4-triazole (Taz) and oxalic acid (Oxac) at 453 K for 12 hours. The crystal structure was determined by the Rietveld method. The as-synthesized ZOTW2.5 was pretreated at 383 K and 1 mPa for tpt h, ZOTWx(tpth). ZOTWx(≥3h) showed Type I adsorption isotherm for N2 at 77 K having the saturation amount (Vs) of 180 mg/g, but that pretreated shortly showed only 1/10 in Vs...
January 3, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28045433/functions-and-epigenetic-regulation-of-wwox-in-bone-metastasis-from-breast-carcinoma-comparison-with-primary-tumors
#14
REVIEW
Paola Maroni, Emanuela Matteucci, Paola Bendinelli, Maria Alfonsina Desiderio
Epigenetic mechanisms influence molecular patterns important for the bone-metastatic process, and here we highlight the role of WW-domain containing oxidoreductase (Wwox). The tumor-suppressor Wwox lacks in almost all cancer types; the variable expression in osteosarcomas is related to lung-metastasis formation, and exogenous Wwox destabilizes HIF-1α (subunit of Hypoxia inducible Factor-1, HIF-1) affecting aerobic glycolysis. Our recent studies show critical functions of Wwox present in 1833-osteotropic clone, in the corresponding xenograft model, and in human bone metastasis from breast carcinoma...
January 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28042766/insights-into-the-regulation-of-yap-taz-from-cellular-systems-and-mouse-models
#15
Wei Du, Wen Du, Mian Wan, Xuedong Zhou, Xin Xu, Liwei Zheng
The Hippo signaling pathway serves as a main regulator of tissue growth and organ size through the moderation of cell cycle dynamics across many different species. In mammals, the two downstream transcriptional regulators of this pathway are Yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ). Recent studies found in addition to the core Hippo signaling pathway, other signaling pathways can also regulate YAP/TAZ activity, either directly or through crosstalk with the Hippo pathway...
January 2, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28035075/the-hippo-signaling-pathway-provides-novel-anti-cancer-drug-targets
#16
REVIEW
June Sung Bae, Sun Mi Kim, Ho Lee
The Hippo signaling pathway plays a crucial role in cell proliferation, apoptosis, differentiation, and development. Major effectors of the Hippo signaling pathway include the transcriptional co-activators Yes-associated protein 1 (YAP) and WW domain-containing transcription regulator protein 1 (TAZ). The transcriptional activities of YAP and TAZ are affected by interactions with proteins from many diverse signaling pathways as well as responses to the external environment. High YAP and TAZ activity has been observed in many cancer types, and functional dysregulation of Hippo signaling enhances the oncogenic properties of YAP and TAZ and promotes cancer development...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28018973/inactivation-of-abl-kinases-suppresses-non-small-cell-lung-cancer-metastasis
#17
Jing Jin Gu, Clay Rouse, Xia Xu, Jun Wang, Mark W Onaitis, Ann Marie Pendergast
Current therapies to treat non-small cell lung carcinoma (NSCLC) have proven ineffective owing to transient, variable, and incomplete responses. Here we show that ABL kinases, ABL1 and ABL2, promote metastasis of lung cancer cells harboring EGFR or KRAS mutations. Inactivation of ABL kinases suppresses NSCLC metastasis to brain and bone, and other organs. ABL kinases are required for expression of prometastasis genes. Notably, ABL1 and ABL2 depletion impairs extravasation of lung adenocarcinoma cells into the lung parenchyma...
December 22, 2016: JCI Insight
https://www.readbyqxmd.com/read/28004182/cdk5rap2-interaction-with-components-of-the-hippo-signaling-pathway-may-play-a-role-in-primary-microcephaly
#18
Salil K Sukumaran, Maria Stumpf, Sarah Salamon, Ilyas Ahmad, Kurchi Bhattacharya, Sarah Fischer, Rolf Müller, Janine Altmüller, Birgit Budde, Holger Thiele, Muhammad Tariq, Naveed Altaf Malik, Peter Nürnberg, Shahid Mahmood Baig, Muhammad Sajid Hussain, Angelika A Noegel
Autosomal recessive primary microcephaly (MCPH) is characterized by a substantial reduction in brain size but with normal architecture. It is often linked to mutations in genes coding for centrosomal proteins; however, their role in brain size regulation is not completely understood. By combining homozygosity mapping and whole-exome sequencing in an MCPH family from Pakistan, we identified a novel mutation (XM_011518861.1; c.4114C > T) in CDK5RAP2, the gene associated with primary microcephaly-3 (MCPH3), leading to a premature stop codon (p...
December 21, 2016: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28003206/a-moderate-increase-in-dietary-zinc-reduces-dna-strand-breaks-in-leukocytes-and-alters-plasma-proteins-without-changing-plasma-zinc-concentrations
#19
Sarah J Zyba, Swapna V Shenvi, David W Killilea, Tai C Holland, Elijah Kim, Adrian Moy, Barbara Sutherland, Virginia Gildengorin, Mark K Shigenaga, Janet C King
BACKGROUND: Food fortification has been recommended to improve a population's micronutrient status. Biofortification techniques modestly elevate the zinc content of cereals, but few studies have reported a positive impact on functional indicators of zinc status. OBJECTIVE: We determined the impact of a modest increase in dietary zinc that was similar to that provided by biofortification programs on whole-body and cellular indicators of zinc status. DESIGN: Eighteen men participated in a 6-wk controlled consumption study of a low-zinc, rice-based diet...
December 21, 2016: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28003126/emerging-role-of-hippo-signalling-in-pancreatic-biology-yap-re-expression-and-plausible-link-to-islet-cell-apoptosis-and-replication
#20
REVIEW
Anjana Sharma, Veera Ganesh Yerra, Ashutosh Kumar
Diabetes mellitus is an ailment that develops when the functional capacity of the pancreas does not meet the metabolic requirements of the whole body, either due to insulin insufficiency or resistance to insulin action. Current therapies that control glycaemia are limited by their unwanted effects or their inability to prevent the development of long-term complications. Regeneration and replacement of beta cell therapies are shaping the goals of future management of diabetes. The Hippo pathway, first discovered in Drosophila melanogaster, plays a vital role in controlling the organ size...
December 18, 2016: Biochimie
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