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https://www.readbyqxmd.com/read/28527754/hippo-signalling-in-intestinal-regeneration-and-cancer
#1
REVIEW
Alex Gregorieff, Jeffrey L Wrana
The Hippo pathway is a unique signalling module that regulates cell-specific transcriptional responses and responds to a wide range of intrinsic and extrinsic cues. Besides its classical role in restricting tissue size during development, Hippo signalling is now recognized to control numerous processes including cell proliferation, survival, cell fate determination, epithelial-to-mesenchymal transitions and cell migration. Because of its highly dynamic nature, the intestinal epithelium has served as an exceptional model to study the complex roles of Hippo signalling...
May 18, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28524356/association-between-yap-expression-in-neoplastic-and-non-neoplastic-breast-tissue-with-arsenic-urinary-levels
#2
Gladis Michel-Ramirez, Rogelio Recio-Vega, Guadalupe Ocampo-Gomez, Eduardo Palacios-Sanchez, Manuel Delgado-Macias, Manuel Delgado-Gaona, Robert Clark Lantz, Jay Gandolfi, Tania Gonzalez-Cortes
The Hippo pathway regulates cell proliferation and apoptosis and it has been noted that loss of critical components of this pathway can lead to uncontrolled cell growth. Yes-associated protein (YAP) is an important component of this Hippo pathway because YAP is the nuclear effector of the Hippo tumor suppressor pathway and it is crucial for the response to oxidative stress induced by cellular process and by different xenobiotics, including arsenic. It has been proposed that YAP dysregulation can contribute to a malignant cellular phenotype acting as both a tumor suppressor and an oncogene...
May 19, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28515914/analysis-of-the-function-of-microrna-375-in-humans-using-bioinformatics
#3
Xiaohua Chen, Baoxia Li, Rongcheng Luo, Sina Cai, Cao Zhang, Xiaolong Cao
MicroRNA-375 (miR-375) is expressed at low levels in many types of solid tumor, particularly in gastrointestinal tumors. It is considered to be important in the development of cancer and certain diseases. Thus, more detailed knowledge is required on the particular functions of miR-375. miRs function by regulating target genes. Therefore, in the current study, miRWalk (which includes the data from 10 prediction software programs) was used to predict the target genes of miR-375. The genes, which were co-predicted using five different software programs were further analyzed using Database for Annotation, Visualization and Integrated Discovery online software [including gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis]...
May 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28515457/crystal-structure-of-taz-tead-complex-reveals-a-distinct-interaction-mode-from-that-of-yap-tead-complex
#4
Hung Yi Kristal Kaan, Siew Wee Chan, Siew Kim Joyce Tan, Fusheng Guo, Chun Jye Lim, Wanjin Hong, Haiwei Song
The Hippo pathway is a tumor suppressor pathway that is implicated in the regulation of organ size. The pathway has three components: the upstream regulatory factors, the kinase core, and the downstream transcriptional machinery, which consists of YAP, TAZ (transcription co-activators) and TEAD (transcription factor). Formation of YAP/TAZ-TEAD complexes leads to the transcription of growth-promoting genes. Herein, we report the crystal structure of TAZ-TEAD4 complex, which reveals two binding modes. The first is similar to the published YAP-TEAD structure...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28514643/yorkie-regulates-epidermal-wound-healing-in-drosophila-larvae-independently-of-cell-proliferation-and-apoptosis
#5
Chang-Ru Tsai, Aimee E Anderson, Sirisha Burra, Juyeon Jo, Michael J Galko
Yorkie (Yki), the transcriptional co-activator of the Hippo signaling pathway, has well-characterized roles in balancing apoptosis and cell division during organ growth control. Yki is also required in diverse tissue regenerative contexts. In most cases this requirement reflects its well-characterized roles in balancing apoptosis and cell division. Whether Yki has repair functions outside of the control of cell proliferation, death, and growth is not clear. Here we show that Yki and Scalloped (Sd) are required for epidermal wound closure in the Drosophila larval epidermis...
May 14, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28504812/overexpression-of-the-yap1-oncogene-in-clear-cell-renal-cell-carcinoma-is-associated-with-poor-outcome
#6
Agnieszka Rybarczyk, Jakub Klacz, Agata Wronska, Marcin Matuszewski, Zbigniew Kmiec, Piotr M Wierzbicki
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of RCC (70-80%). Yes-associated protein 1 (YAP1) protein is a nuclear effector of the Hippo pathway and acts as a transcriptional co-activator of genes involved in the processes of growth and development of tissues. Hippo signaling, with its key kinases, MST2 and large tumor suppressor kinase 1 (LATS1), plays a significant role in the negative regulation of the amount and activity of YAP1 protein. Components of the Hippo pathway and YAP1 levels are frequently dysregulated in a variety of tumors, suggestive of their possible involvement in carcinogenesis...
May 15, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28504697/the-transcriptional-coactivator-taz-regulates-reciprocal-differentiation-of-th17-cells-and-treg-cells
#7
Jing Geng, Shujuan Yu, Hao Zhao, Xiufeng Sun, Xun Li, Ping Wang, Xiaolin Xiong, Lixin Hong, Changchuan Xie, Jiahui Gao, Yiran Shi, Jiaqi Peng, Randy L Johnson, Nengming Xiao, Linrong Lu, Jiahuai Han, Dawang Zhou, Lanfen Chen
An imbalance in the lineages of immunosuppressive regulatory T cells (Treg cells) and the inflammatory TH17 subset of helper T cells leads to the development of autoimmune and/or inflammatory disease. Here we found that TAZ, a coactivator of TEAD transcription factors of Hippo signaling, was expressed under TH17 cell-inducing conditions and was required for TH17 differentiation and TH17 cell-mediated inflammatory diseases. TAZ was a critical co-activator of the TH17-defining transcription factor RORγt. In addition, TAZ attenuated Treg cell development by decreasing acetylation of the Treg cell master regulator Foxp3 mediated by the histone acetyltransferase Tip60, which targeted Foxp3 for proteasomal degradation...
May 15, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28504269/yap-regulates-cell-mechanics-by-controlling-focal-adhesion-assembly
#8
Giorgia Nardone, Jorge Oliver-De La Cruz, Jan Vrbsky, Cecilia Martini, Jan Pribyl, Petr Skládal, Martin Pešl, Guido Caluori, Stefania Pagliari, Fabiana Martino, Zuzana Maceckova, Marian Hajduch, Andres Sanz-Garcia, Nicola Maria Pugno, Gorazd Bernard Stokin, Giancarlo Forte
Hippo effectors YAP/TAZ act as on-off mechanosensing switches by sensing modifications in extracellular matrix (ECM) composition and mechanics. The regulation of their activity has been described by a hierarchical model in which elements of Hippo pathway are under the control of focal adhesions (FAs). Here we unveil the molecular mechanism by which cell spreading and RhoA GTPase activity control FA formation through YAP to stabilize the anchorage of the actin cytoskeleton to the cell membrane. This mechanism requires YAP co-transcriptional function and involves the activation of genes encoding for integrins and FA docking proteins...
May 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28502290/deubiquitinase-yod1-the-potent-activator-of-yap-in-hepatomegaly-and-liver-cancer
#9
Youngeun Kim, Eek-Hoon Jho
The advances of our understanding in the Hippo signaling as a key regulatory pathway of proliferation and apoptosis have provided mechanical insights for controlling organ size and tumorigenicity. Recently, much attention was given to the regulation of LATS1/2 (large tumor suppressor) kinases that phosphorylate YAP/TAZ, a transcriptional co-activator in the Hippo pathway, and control the level and nuclear localization of YAP/TAZ. In our recent work, we showed that deubiquitinase YOD1 stabilizes ITCH and facilitates ITCH-mediated LATS1/2 ubiquitination and degradation, which results in increased YAP/TAZ level...
May 15, 2017: BMB Reports
https://www.readbyqxmd.com/read/28501006/liquid-chromatography-mass-spectrometry-based-quantitative-proteomics-analysis-reveals-chondroprotective-effects-of-astragaloside-iv-in-interleukin-1%C3%AE-induced-sw1353-chondrocyte-like-cells
#10
Huali Luo, Ling Yao, Yudi Zhang, Rongheng Li
OBJECTIVE: Chondrocyte apoptosis played a key role on the progression of Osteoarthritis (OA). Safe and effective drugs are urgently needed for the treatment of OA. Previous study reported that Astragaloside IV (ASG-IV) had exerted a protective effect against articular cartilage degeneration by promoting rapid proliferation of chondrocyte. Therefore, the aim of our study is to explore the effects and mechanisms of ASG-IV in chondrocyte apoptosis. METHODS: Isobaric Tags For Relative And Absolute Quantitation (iTRAQ)-based quantitative proteomics was used to quantitatively detect and map proteins in SW1353 chondrocyte-like cells pre-treated with ASG-IV or interleukin-1β (IL-1β) or ASG-IV+IL-1β...
May 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28500848/the-long-noncoding-rna-hotair-activates-the-hippo-pathway-by-directly-binding-to-sav1-in-renal-cell-carcinoma
#11
Guanghui Hu, Binbin Dong, Jingwei Zhang, Wei Zhai, Tiancheng Xie, Bisheng Huang, Chi Huang, Xudong Yao, Junhua Zheng, Jianping Che, Yun-Fei Xu
The long noncoding RNA HOTAIR promotes the development and progression of several tumors. Here, the clinical significance and role of HOTAIR in renal cell carcinoma (RCC) tumorigenesis were explored. The results showed that increased expression of HOTAIR predicted a poor prognosis of RCC after surgery. HOTAIR promoted RCC cell proliferation and growth in vitro and in vivo. The expressions of HOTAIR and Salvador homolog 1 (SAV1) were inversely correlated in clinical RCC samples. HOTAIR downregulated SAV1 by directly binding to the SAV1 protein and enhanced histone H3K27 methylation...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28498841/awareness-and-attitudes-towards-anthrax-and-meat-consumption-practices-among-affected-communities-in-zambia-a-mixed-methods-approach
#12
Doreen Chilolo Sitali, Chisoni Mumba, Eystein Skjerve, Oliver Mweemba, Consolata Kabonesa, Mwinyi Omary Mwinyi, Luke Nyakarahuka, John Bwalya Muma
BACKGROUND: In Zambia, human anthrax cases often occur following cases of animal anthrax. Human behaviour has been implicated in this transmission. The objective of the study was to explore human behavioural patterns that may contribute to outbreaks of anthrax among affected communities. METHODS: A mixed methods study was conducted in four districts of Zambia from November 2015 to February 2016. A cross sectional survey involving 1,127 respondents, six focus group discussions and seven key informant interviews with professional staff were conducted...
May 12, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28498797/natb-mediated-protein-n-%C3%AE-terminal-acetylation-is-a-potential-therapeutic-target-in-hepatocellular-carcinoma
#13
Leire Neri, Marta Lasa, Alberto Elosegui-Artola, Delia D'Avola, Beatriz Carte, Cristina Gazquez, Sara Alve, Pere Roca-Cusachs, Mercedes Iñarrairaegui, Jose Herrero, J Prieto, Bruno Sangro, Rafael Aldabe
The identification of new targets for systemic therapy of hepatocellular carcinoma (HCC) is an urgent medical need. Recently, we showed that hNatB catalyzes the N-α-terminal acetylation of 15% of the human proteome and that this action is necessary for proper actin cytoskeleton structure and function. In tumors, cytoskeletal changes influence motility, invasion, survival, cell growth and tumor progression, making the cytoskeleton a very attractive antitumor target. Here, we show that hNatB subunits are upregulated in in over 59% HCC tumors compared to non-tumor tissue and that this upregulation is associated with microscopic vascular invasion...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28493234/exploration-of-involved-key-genes-and-signaling-diversity-in-brain-tumors
#14
REVIEW
Mojdeh Mahdian Nasser, Parvin Mehdipour
Brain tumors are becoming a major cause of death. The classification of brain tumors has gone through restructuring with regard to some criteria such as the presence or absence of a specific genetic alteration in the 2016 central nervous system World Health Organization update. Two categories of genes with a leading role in tumorigenesis and cancer induction include tumor suppressor genes and oncogenes; tumor suppressor genes are inactivated through a variety of mechanisms that result in their loss of function...
May 10, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28492365/the-hippo-pathway-effector-yap-is-an-essential-regulator-of-ductal-progenitor-patterning-in-the-mouse-submandibular-gland
#15
Aleksander D Szymaniak, Rongjuan Mi, Shannon E McCarthy, Adam C Gower, Taylor L Reynolds, Michael Mingueneau, Maria Kukuruzinska, Xaralabos Varelas
Salivary glands, such as submandibular glands (SMGs), are composed of branched epithelial ductal networks that terminate in acini that together produce, transport and secrete saliva. Here, we show that the transcriptional regulator Yap, a key effector of the Hippo pathway, is required for the proper patterning and morphogenesis of SMG epithelium. Epithelial deletion of Yap in developing SMGs results in the loss of ductal structures, arising from reduced expression of the EGF family member Epiregulin, which we show is required for the expansion of Krt5/Krt14-positive ductal progenitors...
May 11, 2017: ELife
https://www.readbyqxmd.com/read/28487958/effects-of-taz-on-human-dental-pulp-stem-cell-proliferation-and-migration
#16
Songbo Tian, Xiaochao Tian, Yanping Liu, Fusheng Dong, Jie Wang, Xuqian Liu, Zhiyong Zhang, Huizhen Chen
Transcriptional coactivator with PDZ‑binding motif (TAZ) acts as the key downstream regulatory target in the Hippo signaling pathway. TAZ overexpression has been reported to promote cellular proliferation and induce epithelial‑mesenchymal transition in human mammary epithelial cells. However, the effects of TAZ in the regulation of human dental pulp stem cell (hDPSC) proliferation and migration, as well as the molecular mechanisms underlying its actions, remain to be elucidated. The present study demonstrated that TAZ was expressed in hDPSCs...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28487017/yap-mediates-human-decidualization-of-the-uterine-endometrial-stromal-cells
#17
Hengxi Chen, Yong Song, Shiyuan Yang, Jing Fu, Xue Feng, Wei Huang
INTRODUCTION: The decidualization of uterine endometrial stromal cells (ESCs) is critical for the successful establishment and maintenance of pregnancy and involves extensive cell proliferation and differentiation. A newly established signaling pathway, the Hippo/Yes-associated protein (YAP) pathway, plays a critical role in these proliferation processes. Our previous study demonstrated that YAP is expressed in human ESCs. However, its role in decidualization remains unclear. The objective of the present study was to explore the role of YAP in the decidualization of human ESCs...
May 2017: Placenta
https://www.readbyqxmd.com/read/28486190/icariin-stimulates-osteogenic-differentiation-of-rat-bone-marrow-stromal-stem-cells-by-increasing-taz-expression
#18
QiuShi Wei, MinCong He, MeiHui Chen, ZhenQiu Chen, Fan Yang, HaiBin Wang, Jin Zhang, Wei He
Icariin, the major ingredient of Herba Epimedii, promotes the osteogenic differentiation of rat bone marrow stromal cells (rBMSCs) and exerts protective effects against bone loss and increases bone regeneration, but the underlying signaling pathway by which icariin affects osteogenic differentiation remain unclear. Transcriptional coactivator with PDZ-binding motif (TAZ) is a transcriptional modulator of the Hippo signaling pathway, which plays an important role in the osteogenic differentiation of BMSCs by activating Runx2 gene during the terminal osteogenic differentiation...
May 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28486106/hippo-signaling-suppresses-cell-ploidy-and-tumorigenesis-through-skp2
#19
Shihao Zhang, Qinghua Chen, Qingxu Liu, Yuxi Li, Xiufeng Sun, Lixin Hong, Suyuan Ji, Chengyan Liu, Jing Geng, Weiji Zhang, Zhonglei Lu, Zhen-Yu Yin, Yuanyuan Zeng, Kwang-Huei Lin, Qiao Wu, Qiyuan Li, Keiko Nakayama, Keiich I Nakayama, Xianming Deng, Randy L Johnson, Liang Zhu, Daming Gao, Lanfen Chen, Dawang Zhou
Polyploidy can lead to aneuploidy and tumorigenesis. Here, we report that the Hippo pathway effector Yap promotes the diploid-polyploid conversion and polyploid cell growth through the Akt-Skp2 axis. Yap strongly induces the acetyltransferase p300-mediated acetylation of the E3 ligase Skp2 via Akt signaling. Acetylated Skp2 is exclusively localized to the cytosol, which causes hyper-accumulation of the cyclin-dependent kinase inhibitor p27, leading to mitotic arrest and subsequently cell polyploidy. In addition, the pro-apoptotic factors FoxO1/3 are overly degraded by acetylated Skp2, resulting in polyploid cell division, genomic instability, and oncogenesis...
May 8, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28483529/tead1-mediates-the-oncogenic-activities-of-hippo-yap1-signaling-in-osteosarcoma
#20
Jiwei Chai, Shijie Xu, Fengbo Guo
Hippo signaling pathway is an evolutionarily conserved developmental network that governs the downstream transcriptional co-activators, YAP and TAZ, which bind to and activate the output of TEADs that responsible for cell proliferation, apoptosis, and stem cell self renewal. Emerging evidence has shown the tumor suppressor properties of Hippo signaling. However, limited knowledge is available concerning the downstream transcription factors of Hippo pathway in osteosarcoma (OS). In this study, we demonstrated that TEAD1 was the major transcription factor of Hippo signaling pathway in OS...
May 5, 2017: Biochemical and Biophysical Research Communications
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