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Weijie Li, Shicai Dong, Wei Wei, Guangxiu Wang, Anling Zhang, Peiyu Pu, Zhifan Jia
The transcriptional coactivator with PDZ-binding motif (TAZ) is one of the important downstream effectors of Hippo pathway. In this study, the potential implication of TAZ in gliomagenesis was explored. TAZ expression was identified to be upregulated in glioma specimens and positively correlated with tumor grade. Meanwhile, its expression in nucleus was increased more significantly with the ascending order of tumor grade. Knocking down TAZ inhibited glioma cell proliferation, invasion and promoted apoptosis...
October 13, 2016: Oncotarget
Xiuxia Zhou, Jingna Su, Shaoyan Feng, Lixia Wang, Xuyuan Yin, Jingzhe Yan, Zhiwei Wang
Pancreatic cancer (PC) is one of the most aggressive human malignancies worldwide and is the fourth leading cause of cancer-related deaths. Curcumin (diferuloylmethane) is a polyphenol derived from the Curcuma longa plant. Certain studies have demonstrated that curcumin exerts its anti-tumor function in a variety of human cancers including PC, via targeting multiple therapeutically important cancer signaling pathways. However, the detailed molecular mechanisms are not fully understood. Two transcriptional co-activators, YAP (Yes-associated protein) and its close paralog TAZ (transcriptional coactivator with PDZ-binding motif) exert oncogenic activities in various cancers...
October 12, 2016: Oncotarget
Takaaki Higashi, Hiromitsu Hayashi, Yuki Kitano, Kensuke Yamamura, Takayoshi Kaida, Kota Arima, Katsunobu Taki, Shigeki Nakagawa, Hirohisa Okabe, Hidetoshi Nitta, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Toru Beppu, Hideo Baba
Diabetes and obesity are associated with non-alcoholic steatohepatitis and an increased incidence of hepatocellular carcinoma (HCC). TAZ and YAP are equivalently placed downstream effectors of the Hippo pathway with oncogenic roles in human cancers. Statins are commonly used to patients with metabolic problems as hypercholesterolemia. Statins also have anti-cancer properties, and the cross-talk between mevalonate pathway and Hippo pathway was known. The aim of this study is to confirm the statin's anti-cancer effects on HCC cells and its survival benefits in HCC patients with curative surgery...
November 2016: Medical Oncology
Sarah E Petite, Seth R Bauer, Jessica E Bollinger, Christine L Ahrens, Lisa M Harinstein
STUDY OBJECTIVE: It is unknown if beta-lactam monotherapy is sufficient for complicated intra-abdominal infections or if broader coverage is required, such as with vancomycin. This study sought to determine the clinical outcomes of piperacillin/tazobactam monotherapy compared to combination therapy with vancomycin and piperacillin/tazobactam for complicated intra-abdominal infections among patients within a surgical intensive care unit. DESIGN: Retrospective cohort study...
October 11, 2016: Pharmacotherapy
Susanne Muehlich, Margot Rehm, Astrid Ebenau, Margarete Goppelt-Struebe
Changes in cell morphology that involve alterations of the actin cytoskeleton are a hallmark of diseased renal tubular epithelial cells. While the impact of actin remodeling on gene expression has been analyzed in many model systems based on cell lines, this study investigated human primary tubular epithelial cells isolated from healthy parts of tumor nephrectomies. Latrunculin B (LatB) and cytochalasin D (CytoD) were used to modulate G-actin levels in a receptor-independent manner. Both compounds (at 0.5μM) profoundly altered F-actin structures in a Rho kinase-dependent manner, but only CytoD strongly induced the pro-fibrotic factor CTGF (connective tissue growth factor)...
October 7, 2016: Cellular Signalling
Hao Zhang, Decheng Geng, Jian Gao, Yanhua Qi, Yi Shi, Yan Wang, Yang Jiang, Yu Zhang, Jiale Fu, Yu Dong, Shangfeng Gao, Rutong Yu, Xiuping Zhou
Dysregulation of Hippo/YAP signaling leads to aberrant cell growth and neoplasia. Although the roles and regulation of Hippo/YAP signaling were extensively studied in cancer biology recently, study systematically checking the expression pattern of core components of this pathway at the tumor tissue level remains lacking. In this study, we thoroughly examined the profile of core components of Hippo/YAP signaling in patient specimens both at the mRNA and at protein levels. We found that the mRNA level of YAP1/TAZ and their target genes, CRY61, CTGF, and BIRC5, was remarkably amplified in glioma tissues...
October 7, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Ruyi Zou, Da Li, Gang Wang, Mo Zhang, Yili Zhao, Zeyu Yang
The transcriptional coactivator with PDZ-binding motif (TAZ) functions as a downstream regulatory target in the Hippo signaling pathway that plays various roles. We previously developed a cell-based assay and identified the TAZ activator IBS008738 as a potential therapeutic target for glucocorticoid-induced atrophy. To further explore the application of IBS008738 in various muscle-related diseases, we examined the function of IBS008738 in inflammatory cytokine-mediated mouse muscle responses after traumatic brain injury (TBI)...
October 7, 2016: Inflammation
Qiong Duan, Yi Xiao, Lingyan Zhu, Zhenzhen Liu, Xiaoxiao Mao, Zhengxiang Zhou, Chaonan Liao, Jinxing Cai, Fulian Huang, Zehao Liu, Jian Zeng, Ke Xia, Cheng Chang, Jun Qi, Zihua Chen, He Huang, Tianlun Yang
Transcriptional coactivator with PDZ-binding motif (TAZ) is a key transcriptional mediator of Hippo signaling that has been recently reported to mediate Wnt-activated transcription and serve as a component to suppress canonical Wnt/β-catenin activity. The Bromodomain and Extra-terminal domain (BET) family of proteins can recognize the acetylated lysine chain on histones and plays a critical role in transcriptional regulation. However, the mechanisms underlying transcriptional repression by the BET bromodomain are poorly understood...
October 4, 2016: Biochimica et Biophysica Acta
Anna Di Benedetto, Marcella Mottolese, Francesca Sperati, Cristiana Ercolani, Luigi Di Lauro, Laura Pizzuti, Patrizia Vici, Irene Terrenato, Abeer M Shaaban, Sreekumar Sundara-Rajan, Matthew P Humphries, Maddalena Barba, Valerie Speirs, Ruggero De Maria, Marcello Maugeri-Saccà
Male breast cancer (MBC) is a rare hormone-driven disease often associated with obesity. HMG-CoAR is the central enzyme of the mevalonate pathway, a molecular route deputed to produce cholesterol and steroid-based hormones. HMG-CoAR regulates the oncogenic Hippo transducers TAZ/YAP whose expression was previously associated with shorter survival in MBC. 225 MBC samples were immunostained for HMG-CoAR and 124 were considered eligible for exploring its relationship with hormone receptors (ER, PgR, AR), Hippo transducers and survival outcomes...
October 7, 2016: Scientific Reports
Naomi Sugimoto, Yuka Yamagishi, Hiroshige Mikamo
The isolation rate of extended-spectrum β-lactamase (ESBL)-producing bacteria have been increasing in Japan. While the efficacy of piperacillin/tazobactam (PIPC/TAZ) for ESBL-producing bacteria is controversial, carbapenems have generally been shown to be effective. The aim of this study was to determine whether the current Clinical and Laboratory Standards Institute susceptibility breakpoint of ≤16/4 μg/mL PIPC/TAZ predicts the clinical usefulness for bacteremia caused by ESBL-producing Enterobacteriaceae...
September 28, 2016: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
Hejiao Bian, Jean Z Lin, Chendi Li, Stephen R Farmer
OBJECTIVE: Arising from common progenitors in the bone marrow, adipogenesis and osteogenesis are closely associated yet mutually exclusive during bone marrow mesenchymal stem cell (BMSC) development. Previous studies have shown that morphological changes can affect the early commitment of pluripotent BMSCs to the adipose versus osteoblastic lineage via modulation of RhoA activity. The RhoA pathway regulates actin polymerization to promote the incorporation of globular actin (G-actin) into filamentous actin (F-actin)...
October 2016: Molecular Metabolism
Ni Xu, Ming-Zheng Wu, Xue-Ting Deng, Ping-Chuan Ma, Ze-Hua Li, Lei Liang, Meng-Fan Xia, Dong Cui, Duan-Duan He, Yuan Zong, Zhong Xie, Xue-Jun Song
UNLABELLED: Neuropathic pain, often caused by nerve injury, is a major clinical challenge. Mechanisms that underlie neuropathic pain remain elusive and effective medications are limited. Numerous investigations of pain mechanisms have focused on alterations and phenotypic switches of the nociceptive transmitters and modulators, as well as on their receptors and downstream signaling pathways that have already exerted roles in the pain processes of mature nervous systems. We have demonstrated recently that nerve injury may elicit neuronal alterations that recapitulate events occurring during development...
September 28, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Kuei-Chun Wang, Yi-Ting Yeh, Phu Nguyen, Elaine Limqueco, Jocelyn Lopez, Satenick Thorossian, Kun-Liang Guan, Yi-Shuan J Li, Shu Chien
The focal nature of atherosclerotic lesions suggests an important role of local hemodynamic environment. Recent studies have demonstrated significant roles of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in mediating mechanotransduction and vascular homeostasis. The objective of this study is to investigate the functional role of YAP/TAZ in the flow regulation of atheroprone endothelial phenotypes and the consequential development of atherosclerotic lesions. We found that exposure of cultured endothelial cells (ECs) to the atheroprone disturbed flow resulted in YAP/TAZ activation and translocation into EC nucleus to up-regulate the target genes, including cysteine-rich angiogenic inducer 61 (CYR61), connective tissue growth factor (CTGF), and ankyrin repeat domain 1 (ANKRD1)...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Yin Xu, Kaiqiang Wang, Qin Yu
FRMD6 is an Ezrin/Radixin/Moesin (ERM) family protein and a human homologue of Drosophila expanded (ex). Ex functions in parallel of Drosophila merlin at upstream of the Hippo signaling pathway that controls proliferation, apoptosis, tissue regeneration, and tumorigenesis. Even though the core kinase cascade (MST1/2-Lats1/2-YAP/TAZ) of the Hippo pathway has been well established, its upstream regulators are not well understood. Merlin promotes activation of the Hippo pathway. However, the effect of FRMD6 on the Hippo pathway is controversial...
September 20, 2016: Oncotarget
Qiang Zhao, Yi-Ran Ren, Qing-Jie Wang, Xiao-Fei Wang, Chun-Xiang You, Yu-Jin Hao
Fe homeostasis is crucial for plant growth and development. A network of bHLH transcription factors (TFs) positively regulates Fe uptake during iron deficiency. However, their upregulation or overexpression leads to Fe overload and ROS generation, thereby damaging the plants. Here, we found that two BTB/TAZ proteins, MdBT1 and MdBT2, interact with the MbHLH104 protein in apple. In addition, the function of MdBT2 was characterized as a regulator of MdbHLH104 degradation via ubiquitination and the 26S proteosome pathway, thereby controlling the activity of plasma membrane H+-ATPases and the acquisition of iron...
September 22, 2016: Plant Physiology
Helen McNeill, Antoine Reginensi
In the kidney, formation of the functional filtration units, the nephrons, is essential for postnatal life. During development, mesenchymal progenitors tightly regulate the balance between self-renewal and differentiation to give rise to all nephron epithelia. Here, we investigated the functions of the Hippo pathway serine/threonine-protein kinases Lats1 and Lats2, which phosphorylate and inhibit the transcriptional coactivators Yap and Taz, in nephron progenitor cells. Genetic deletion of Lats1 and Lats2 in nephron progenitors of mice led to disruption of nephrogenesis, with an accumulation of spindle-shaped cells in both cortical and medullary regions of the kidney...
September 19, 2016: Journal of the American Society of Nephrology: JASN
Tito Panciera, Luca Azzolin, Atsushi Fujimura, Daniele Di Biagio, Chiara Frasson, Silvia Bresolin, Sandra Soligo, Giuseppe Basso, Silvio Bicciato, Antonio Rosato, Michelangelo Cordenonsi, Stefano Piccolo
The ability to induce autologous tissue-specific stem cells in culture could have a variety of applications in regenerative medicine and disease modeling. Here we show that transient expression of exogenous YAP or its closely related paralogue TAZ in primary differentiated mouse cells can induce conversion to a tissue-specific stem/progenitor cell state. Differentiated mammary gland, neuronal, and pancreatic exocrine cells, identified using a combination of cell sorting and lineage tracing approaches, efficiently convert to proliferating cells with properties of stem/progenitor cells of their respective tissues after YAP induction...
September 9, 2016: Cell Stem Cell
Mattia Zaccarin, Valentina Bosello-Travain, Maria Luisa Di Paolo, Marco Falda, Matilde Maiorino, Giovanni Miotto, Stefano Piccolo, Antonella Roveri, Fulvio Ursini, Rina Venerando, Stefano Toppo
Reversible oxidation of Cys residues is a crucial element of redox homeostasis and signaling. According to a popular concept in oxidative stress signaling, the oxidation of targets of signals can only take place following an overwhelming of the cellular antioxidant capacity. This concept, however, ignores the activation of feedback mechanisms possibly leading to a paradoxical effect. In a model of cancer stem cells (CSC), stably overexpressing the TAZ oncogene, we observed that the increased formation of oxidants is associated with a globally more reduced state of proteins...
September 13, 2016: Archives of Biochemistry and Biophysics
Kati Kemppainen, Nina Wentus, Taru Lassila, Asta Laiho, Kid Törnquist
Sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid which regulates many cancer-related processes, including cellular proliferation. The Hippo signaling pathway consists of a cascade of tumor suppressive kinases Mst1/2 and Lats1/2 and their downstream targets YAP and TAZ which are generally pro-proliferative transcriptional regulators. Direct phosphorylation by Lats1/2 causes inhibition or degradation of YAP/TAZ and down-regulation of their target genes. We found SPC treatment of MDA-MB-435S breast cancer cells to strongly inhibit their proliferation and to induce a sustained Lats2 protein expression (6-24h)...
December 2016: Cellular Signalling
Srijit Das, Seong Lin Teoh
The incidence of lung cancers has increased globally. Increased exposure to tobacco, passive smoking, less consumption of vegetables and fruits and occupational exposure to asbestos, arsenic and chromium are the main risk factors. The pathophysiology of lung cancer is complex and not well understood. Various microRNAs, genes and pathways are associated with lung cancers. The genes involved in lung cancers produce proteins involved in cell growth, differentiation, different cell cycles, apoptosis, immune modulation, tumor spread and progression...
September 7, 2016: Current Drug Targets
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