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https://www.readbyqxmd.com/read/28925394/tissue-inhibitor-of-metalloproteinase-1-promotes-cell-proliferation-through-yap-taz-activation-in-cancer
#1
T Ando, D Charindra, M Shrestha, H Umehara, I Ogawa, M Miyauchi, T Takata
Tissue inhibitor of metalloproteinase-1 (TIMP-1), a member of the TIMP family (TIMP-1 to 4), is highly expressed in various types of cancer and forms a complex with its receptor CD63 and Integrin β1. However, the precise oncogenic mechanism of TIMP-1 remains unclear. Yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ) are transcription co-activators enhancing the transcription of specific genes related to cell proliferation. But the mechanism of aberrant YAP/TAZ activation in cancer is not fully understood...
September 18, 2017: Oncogene
https://www.readbyqxmd.com/read/28891439/the-regulation-of-differentiation-of-mesenchymal-stem-cells-into-skeletal-muscle-a-look-at-signalling-molecules-involved-in-myogenesis
#2
Bethany Hodgson, Reza Mafi, Pouya Mafi, Wasim Khan
Mesenchymal Stem Cells (MSCs) are an attractive option for the development of treatment for musculoskeletal pathologies due to their wide availability, clinical safety and multiple techniques available. Understanding the control of MSC differentiation into skeletal muscle is vital for developing protocols and therapeutic applications that are safe and effective. This paper therefore aims to review the current understanding of factors that regulate the differentiation of MSCs into skeletal muscle. Medline, Embase, Pubmed and Web of Science were searched December 2015 using the terms 'differentia*, skeletal*, skeleton*, myocyt*, myogen* and mesenchym* stem-cell*...
September 6, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28891248/integrin-fak-cdc42-pp1a-signaling-gnaws-at-yap-taz-activity-to-control-incisor-stem-cells
#3
REVIEW
Julia Hicks-Berthet, Xaralabos Varelas
How epithelial tissues are able to self-renew to maintain homeostasis and regenerate in response to injury remains a persistent question. The transcriptional effectors YAP and TAZ are increasingly being recognized as central mediators of epithelial stem cell biology, and a wealth of recent studies have been directed at understanding the control and activity of these factors. Recent work by Hu et al. has added to this knowledge, as they identify an Integrin-FAK-CDC42-PP1A signaling cascade that directs nuclear YAP/TAZ activity in stem cell populations of the mouse incisor, and define convergence on mTORC1 signaling as an important mediator of the proliferation of these cells...
September 11, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28886519/development-and-validation-of-a-liquid-chromatography-tandem-mass-spectrometry-method-for-pharmacokinetic-study-of-tm-53-a-novel-transcriptional-coactivator-with-pdz-binding-motif-taz-modulator
#4
Ha-Yeon Lee, Nak Jeong Kim, Yong Moon Lee, Jin Sook Song, Myung Ae Bae, Sunjoo Ahn
Transcriptional coactivator with PDZ-binding motif (TAZ) is considered an attractive target for osteoporosis, obesity, and muscle regeneration. TM-53, a promising TAZ modulator, was recently introduced, and here, we developed a rapid, precise, and reliable analytical method for TM-53 and characterized its pharmacokinetic properties in rat plasma. The hybrid triple quadrupole/linear ion trap coupled to liquid chromatography method was developed and validated to quantify TM-53. Additionally, TM-53 concentrations in plasma were analyzed, and its pharmacokinetic parameters were calculated by non-compartmental analysis...
August 31, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28881733/positive-regulation-of-taz-expression-by-ebv-lmp1-contributes-to-cell-proliferation-and-epithelial-mesenchymal-transition-in-nasopharyngeal-carcinoma
#5
Jiang He, Feiyu Tang, Liyu Liu, Lin Chen, Jiang Li, Danming Ou, Lu Zhang, Zhi Li, Deyun Feng, Wenzheng Li, Lun-Quan Sun
The Epstein-Barr virus latent membrane protein 1 (LMP1) is an integral membrane protein. LMP1 has been reported to activate the NF-κB and mitogen-activated protein kinase pathways. However, these effects alone are unable to account for the profound oncogenic properties of LMP1. TAZ is one of the nuclear effectors of Hippo-related pathways and highly expressed in many human tumors. Here, we reported that TAZ was frequently expressed in LMP1-positive nasopharyngeal carcinoma. In NPC cell lines, we showed that LMP1 promoted TAZ expression...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877210/tankyrase-inhibitors-suppress-hepatocellular-carcinoma-cell-growth-via-modulating-the-hippo-cascade
#6
Jiaoyuan Jia, Yu Qiao, Maria G Pilo, Antonio Cigliano, Xianqiong Liu, Zixuan Shao, Diego F Calvisi, Xin Chen
Previous data indicate that Tankyrase inhibitors exert anti-growth functions in many cancer cell lines due to their ability to inactivate the YAP protooncogene. In the present manuscript, we investigated the effect of Tankyrase inhibitors on the growth of hepatocellular carcinoma (HCC) cell lines and the molecular mechanisms involved. For this purpose, we performed cell proliferation assay by colony-forming ability in seven human HCC cells subjected to XAV-939 and G007-LK Tankyrase inhibitors. Noticeably, the two Tankyrase inhibitors suppressed the HCC cell growth in a dose-dependent manner...
2017: PloS One
https://www.readbyqxmd.com/read/28870693/therapeutic-targeting-of-taz-and-yap-by-dimethyl-fumarate-in-systemic-sclerosis-fibrosis
#7
Tetsuo Toyama, Agnieszka P Looney, Brendon M Baker, Lukasz Stawski, Paul Haines, Robert Simms, Aleksander D Szymaniak, Xaralabos Varelas, Maria Trojanowska
Systemic sclerosis (scleroderma, SSc) is a devastating fibrotic disease with few treatment options. Fumaric acid esters, including dimethyl fumarate (DMF, Tecfidera®) have shown therapeutic effects in several disease models, prompting us to determine whether DMF is effective as a treatment for SSc dermal fibrosis. We found that DMF blocks the pro-fibrotic effects of TGFβ in SSc skin fibroblasts. Mechanistically, we found that DMF treatment reduced nuclear localization of TAZ and YAP proteins via inhibition of PI3-K/Akt1 pathway...
September 1, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28867699/frequency-of-acute-kidney-injury-caused-by-tazobactam-piperacillin-in-patients-with-pneumonia-and-chronic-kidney-disease-a-retrospective-observational-study
#8
Takeyori Morimoto, Hiroki Nagashima, Yasuko Morimoto, Shogo Tokuyama
 Tazobactam/piperacillin (TAZ/PIPC) is a combination antibiotic frequently used to treat pneumonia. It has recently been reported that TAZ/PIPC worsens renal function in patients with existing renal impairment. Creatinine clearance is generally between 10 and 40 mL/min in Japanese patients, so TAZ/PIPC is given at a dose of 2.25 g three times daily or 4.5 g twice daily. If pneumonia is severe or intractable, the dose frequency may be increased to 2.25 g four times daily and 4.5 g three times daily. We examined the effect of these different dosing regimens on renal function...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28867486/yap-taz-orchestrate-vegf-signaling-during-developmental-angiogenesis
#9
Xiaohong Wang, Aida Freire Valls, Géza Schermann, Ying Shen, Ivan M Moya, Laura Castro, Severino Urban, Gergely M Solecki, Frank Winkler, Lars Riedemann, Rakesh K Jain, Massimilano Mazzone, Thomas Schmidt, Tamás Fischer, Georg Halder, Carmen Ruiz de Almodóvar
Vascular endothelial growth factor (VEGF) is a major driver of blood vessel formation. However, the signal transduction pathways culminating in the biological consequences of VEGF signaling are only partially understood. Here, we show that the Hippo pathway effectors YAP and TAZ work as crucial signal transducers to mediate VEGF-VEGFR2 signaling during angiogenesis. We demonstrate that YAP/TAZ are essential for vascular development as endothelium-specific deletion of YAP/TAZ leads to impaired vascularization and embryonic lethality...
September 11, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28866620/hepatic-hippo-signaling-inhibits-protumoural-microenvironment-to-suppress-hepatocellular-carcinoma
#10
Wantae Kim, Sanjoy Kumar Khan, Yuchen Liu, Ruoshi Xu, Ogyi Park, Yong He, Boksik Cha, Bin Gao, Yingzi Yang
OBJECTIVE: Hippo signalling is a recently identified major oncosuppressive pathway that plays critical roles in inhibiting hepatocyte proliferation, survival and hepatocellular carcinoma (HCC) formation. Hippo kinase (Mst1 and Mst2) inhibits HCC proliferation by suppressing Yap/Taz transcription activities. As human HCC is mainly driven by chronic liver inflammation, it is not clear whether Hippo signalling inhibits HCC by shaping its inflammatory microenvironment. DESIGN: We have established a genetic HCC model by deleting Mst1 and Mst2 in hepatocytes...
September 2, 2017: Gut
https://www.readbyqxmd.com/read/28865751/rhoa-activation-and-nuclearization-marks-loss-of-chondrocyte-phenotype-in-crosstalk-with-wnt-pathway
#11
Ece Öztürk, Evelin Despot-Slade, Michael Pichler, Marcy Zenobi-Wong
De-differentiation comprises a major drawback for the use of autologous chondrocytes in cartilage repair. Here, we investigate the role of RhoA and canonical Wnt signaling in chondrocyte phenotype. Chondrocyte de-differentiation is accompanied by an upregulation and nuclear localization of RhoA. Effectors of canonical Wnt signaling including β-catenin and YAP/TAZ are upregulated in de-differentiating chondrocytes in a Rho-dependent manner. Inhibition of Rho activation with C3 transferase inhibits nuclear localization of RhoA, induces expression of chondrogenic markers on 2D and enhances the chondrogenic effect of 3D culturing...
September 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28855170/a-wide-and-specific-spectrum-of-genetic-variants-and-genotype-phenotype-correlations-revealed-by-next-generation-sequencing-in-patients-with-left-ventricular-noncompaction
#12
Ce Wang, Yukiko Hata, Keiichi Hirono, Asami Takasaki, Sayaka Watanabe Ozawa, Hideyuki Nakaoka, Kazuyoshi Saito, Nariaki Miyao, Mako Okabe, Keijiro Ibuki, Naoki Nishida, Hideki Origasa, Xianyi Yu, Neil E Bowles, Fukiko Ichida
BACKGROUND: Left ventricular noncompaction (LVNC) has since been classified as a primary genetic cardiomyopathy, but the genetic basis is not fully evaluated. The aim of the present study was to identify the genetic spectrum using next-generation sequencing and to evaluate genotype-phenotype correlations in LVNC patients. METHODS AND RESULTS: Using next-generation sequencing, we targeted and sequenced 73 genes related to cardiomyopathy in 102 unrelated LVNC patients...
August 30, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28852375/schwann-cell-development-maturation-and-regeneration-a-focus-on-classic-and-emerging-intracellular-signaling-pathways
#13
REVIEW
Luca Franco Castelnovo, Veronica Bonalume, Simona Melfi, Marinella Ballabio, Deborah Colleoni, Valerio Magnaghi
The development, maturation and regeneration of Schwann cells (SCs), the main glial cells of the peripheral nervous system, require the coordinate and complementary interaction among several factors, signals and intracellular pathways. These regulatory molecules consist of integrins, neuregulins, growth factors, hormones, neurotransmitters, as well as entire intracellular pathways including protein-kinase A, C, Akt, Erk/MAPK, Hippo, mTOR, etc. For instance, Hippo pathway is overall involved in proliferation, apoptosis, regeneration and organ size control, being crucial in cancer proliferation process...
July 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28844657/cytoplasmic-and-nuclear-taz-exert-distinct-functions-in-regulating-primed%C3%A2-pluripotency
#14
Xingliang Zhou, Jean Paul Chadarevian, Bryan Ruiz, Qi-Long Ying
Mouse epiblast stem cells (mEpiSCs) and human embryonic stem cells (hESCs) are primed pluripotent stem cells whose self-renewal can be maintained through cytoplasmic stabilization and retention of β-catenin. The underlying mechanism, however, remains largely unknown. Here, we show that cytoplasmic β-catenin interacts with and retains TAZ, a Hippo pathway effector, in the cytoplasm. Cytoplasmic retention of TAZ promotes mEpiSC self-renewal in the absence of nuclear β-catenin, whereas nuclear translocation of TAZ induces mEpiSC differentiation...
September 12, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28827743/mir-125a-mir-139-and-mir-324-contribute-to-urocortin-protection-against-myocardial-ischemia-reperfusion-injury
#15
Ignacio Díaz, Eva Calderón-Sánchez, Raquel Del Toro, Javier Ávila-Médina, Eva Sánchez de Rojas-de Pedro, Alejandro Domínguez-Rodríguez, Juan Antonio Rosado, Abdelkrim Hmadcha, Antonio Ordóñez, Tarik Smani
Urocortin 1 and 2 (Ucn-1 and Ucn-2) have established protective actions against myocardial ischemia-reperfusion (I/R) injuries. However, little is known about their role in posttranscriptional regulation in the process of cardioprotection. Herein, we investigated whether microRNAs play a role in urocortin-induced cardioprotection. Administration of Ucn-1 and Ucn-2 at the beginning of reperfusion significantly restored cardiac function, as evidenced ex vivo in Langendorff-perfused rat hearts and in vivo in rat subjected to I/R...
August 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28822881/investigating-the-relationship-between-jobs-housing-balance-and-traffic-safety
#16
Chengcheng Xu, Haojie Li, Jingya Zhao, Jun Chen, Wei Wang
This study aimed to investigate the effects of jobs-housing balance on traffic safety. The crash, demographic characteristics, employment, road network, household characteristics and traffic data were collected from the Los Angeles in 2010. One-way ANOVA tests indicated that the jobs-housing ratio significantly affects traffic safety in terms of crash frequency at traffic analysis zone (TAZ). To quantify the safety impacts of jobs-housing balance, the semi-parametric geographically weighted Poisson regression (S-GWPR) was further used to link crash frequency at TAZ with jobs-housing ratio and other contributing factors...
August 17, 2017: Accident; Analysis and Prevention
https://www.readbyqxmd.com/read/28822004/in-vitro-validation-of-the-hippo-pathway-as-a-pharmacological-target-for-canine-mammary-gland-tumors
#17
Samantha Guillemette, Charlène Rico, Philippe Godin, Derek Boerboom, Marilène Paquet
Canine mammary tumors (CMTs) are the most common neoplasms in intact female dogs. Some clinical and molecular similarities between certain CMT subtypes and breast cancer make them a potential model for the study of the human disease. As misregulated Hippo signaling is thought to play an important role in breast cancer development and also occurs in CMTs, we sought to determine if Hippo represents a valid pharmacological target for the treatment of CMTs. Six CMT cell lines were assessed for their expression of the Hippo pathway effectors YAP and TAZ and for their sensitivity to verteporfin, an inhibitor of YAP-mediated transcriptional coactivation...
August 18, 2017: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/28820389/hippo-pathway-brief-overview-of-its-relevance-in-cancer
#18
A L Zygulska, K Krzemieniecki, P Pierzchalski
The Hippo pathway is the major regulator of organ growth and proliferation. Described initially in Drosophila, it is now recognized as one of the most conserved molecular pathways in all metazoan. Recent studies have revealed the Hippo signalling pathway might contribute to tumorigenesis and cancer development. The core components of the Hippo pathway include the mammalian sterile 20-like kinases (MSTs), large tumour suppressor kinases (LATSs), the adaptor proteins Salvador homologue 1 (SAV1, also called WW45) and Mps One Binder kinase activator proteins...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28805663/yap-taz-regulates-sprouting-angiogenesis-and-vascular-barrier-maturation
#19
Jongshin Kim, Yoo Hyung Kim, Jaeryung Kim, Do Young Park, Hosung Bae, Da-Hye Lee, Kyun Hoo Kim, Seon Pyo Hong, Seung Pil Jang, Yoshiaki Kubota, Young-Guen Kwon, Dae-Sik Lim, Gou Young Koh
Angiogenesis is a multistep process that requires coordinated migration, proliferation, and junction formation of vascular endothelial cells (ECs) to form new vessel branches in response to growth stimuli. Major intracellular signaling pathways that regulate angiogenesis have been well elucidated, but key transcriptional regulators that mediate these signaling pathways and control EC behaviors are only beginning to be understood. Here, we show that YAP/TAZ, a transcriptional coactivator that acts as an end effector of Hippo signaling, is critical for sprouting angiogenesis and vascular barrier formation and maturation...
August 14, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28799225/hydrogels-with-reversible-mechanics-to-probe-dynamic-cell-microenvironments
#20
Adrianne M Rosales, Sebastián L Vega, Frank W DelRio, Jason A Burdick, Kristi S Anseth
The relationship between ECM mechanics and cell behavior is dynamic, as cells remodel and respond to changes in their local environment. Most in vitro substrates are static and supraphysiologically stiff; thus, platforms with dynamic and reversible mechanical changes are needed. Herein, we developed hyaluronic acid-based substrates capable of sequential photodegradation and photoinitiated crosslinking reactions to soften and then stiffen the hydrogels over a physiologically relevant range of moduli. Reversible mechanical signaling to adhered cells was demonstrated with human mesenchymal stem cells...
August 10, 2017: Angewandte Chemie
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