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https://www.readbyqxmd.com/read/28720576/deubiquitinating-enzyme-usp9x-suppresses-tumor-growth-via-lats-kinase-and-core-components-of-the-hippo-pathway
#1
Aleksandra Toloczko, Fusheng Guo, Hiu-Fung Yuen, Qing Wen, Stephen Andrew Wood, Yan Shan Ong, Pei Yi Chan, Asfa Alli Shaik, Jayantha Gunaratne, Mark John Dunne, Wanjin Hong, Siew Wee Chan
The core LATS kinases of the Hippo tumor suppressor pathway phosphorylate and inhibit the downstream transcriptional co-activators YAP and TAZ, which are implicated in various cancers. Recent studies have identified various E3 ubiquitin ligases that negatively regulate the Hippo pathway via ubiquitination, yet few deubiquitinating enzymes (DUB) have been implicated. In this study, we report the DUB USP9X is an important regulator of the core kinases of this pathway. USP9X interacted strongly with LATS kinase and to a lesser extent with WW45, KIBRA, and Angiomotin, and LATS co-migrated exclusively with USP9X during gel filtration chromatography analysis...
July 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28717075/clinical-characteristics-of-bacteremia-caused-by-extended-spectrum-beta-lactamase-producing-escherichia-coli-at-a-tertiary-hospital
#2
Hiroki Namikawa, Koichi Yamada, Hiroki Fujimoto, Ken-Ichi Oinuma, Yoshihiro Tochino, Yasuhiko Takemoto, Yukihiro Kaneko, Taichi Shuto, Hiroshi Kakeya
Objective In recent years, infection caused by extended-spectrum beta-lactamase (ESBL)-producing organisms has become an important issue. However, comparative studies of the bacteremia caused by ESBL Enterobacteriaceae and non-ESBL Enterobacteriaceae are extremely rare in Japan. This study aimed to assess the risk factors and prognosis of patients with bacteremia due to ESBL Escherichia coli (E. coli). Methods The medical records of 31 patients with ESBL E. coli bacteremia and 98 patients with non-ESBL E. coli bacteremia who had been admitted to Osaka City University Hospital between January 2011 and June 2015 were retrospectively reviewed...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28710768/panobinostat-sensitizes-kras-mutant-non-small-cell-lung-cancer-to-gefitinib-by-targeting-taz
#3
Wen-Ying Lee, Pin-Cyuan Chen, Wen-Shin Wu, Han-Chung Wu, Chun-Hsin Lan, Yen-Hua Huang, Chia-Hsiung Cheng, Ku-Chung Chen, Cheng-Wei Lin
Mutation of KRAS in non-small cell lung cancer (NSCLC) shows a poor response to epidermal growth factor receptor (EGFR) inhibitors and chemotherapy. Currently, there are no direct anti-KRAS therapies available. Thus, new strategies have emerged for targeting KRAS downstream signaling. Panobinostat is a clinically available histone deacetylase inhibitor for treating myelomas and also shows potentiality in NSCLC. However, the therapeutic efficacy of panobinostat against gefitinib-resistant NSCLC is unclear. In this study, we demonstrated that panobinostat overcame resistance to gefitinib in KRAS-mutant/EGFR-wild type NSCLC...
July 14, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28700335/gtse1-a-novel-tead4-e2f1-target-gene-involved-in-cell-protrusions-formation-in-triple-negative-breast-cancer-cell-models
#4
Stelitano Debora, Peche Leticia Yamila, Dalla Emiliano, Monte Martin, Piazza Silvano, Schneider Claudio
GTSE1 over-expression has been reported as a potential marker for metastasis in various types of malignancies, including breast cancer. Despite this, the transcriptional regulation of this protein and the causes of its misregulation in tumors remain largely unknown. The aims of this work were to elucidate how GTSE1 is regulated at the transcriptional level and to clarify the mechanism underlying GTSE1-dependent cell functions in triple-negative breast cancer (TNBC).Here, we identified GTSE1 as a novel target gene of the TEAD4 transcription factor, highlighting a role for the YAP and TAZ coactivators in the transcriptional regulation of GTSE1...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700334/anti-sstr2-peptide-based-targeted-delivery-of-potent-plga-encapsulated-3-3%C3%A2-diindolylmethane-nanoparticles-through-blood-brain-barrier-prevents-glioma-progression
#5
Stelitano Debora, Peche Leticia Yamila, Dalla Emiliano, Monte Martin, Piazza Silvano, Schneider Claudio
GTSE1 over-expression has been reported as a potential marker for metastasis in various types of malignancies, including breast cancer. Despite this, the transcriptional regulation of this protein and the causes of its misregulation in tumors remain largely unknown. The aims of this work were to elucidate how GTSE1 is regulated at the transcriptional level and to clarify the mechanism underlying GTSE1-dependent cell functions in triple-negative breast cancer (TNBC).Here, we identified GTSE1 as a novel target gene of the TEAD4 transcription factor, highlighting a role for the YAP and TAZ coactivators in the transcriptional regulation of GTSE1...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700256/hippo-pathway-an-emerging-regulator-of-craniofacial-and-dental-development
#6
J Wang, J F Martin
The evolutionarily conserved Hippo signaling pathway is a vital regulator of organ size that fine-tunes cell proliferation, apoptosis, and differentiation. A number of important studies have revealed critical roles of Hippo signaling and its effectors Yap (Yes-associated protein) and Taz (transcriptional coactivator with PDZ binding motif) in tissue development, homeostasis, and regeneration, as well as in tumorigenesis. In addition, recent studies have shown evidence of crosstalk between the Hippo pathway and other key signaling pathways, such as Wnt signaling, that not only regulates developmental processes but also contributes to disease pathogenesis...
July 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28694230/pharmacokinetics-of-piperacillin-tazobactam-in-plasma-peritoneal-fluid-and-peritoneum-of-surgery-patients-and-dosing-considerations-based-on-site-specific-pharmacodynamic-target-attainment
#7
Naoki Murao, Hiroki Ohge, Kazuro Ikawa, Yusuke Watadani, Shinnosuke Uegami, Norifumi Shigemoto, Norimitsu Shimada, Raita Yano, Toshiki Kajihara, Kenichiro Uemura, Yoshiaki Murakami, Norifumi Morikawa, Taijiro Sueda
Piperacillin-tazobactam (PIP-TAZ) is commonly used to treat intraabdominal infections; however, its penetration into abdominal sites is unclear. A pharmacokinetic analysis of plasma, peritoneal fluid, and peritoneum drug concentrations was conducted to simulate dosing regimens needed to attain the pharmacodynamic target in abdominal sites. PIP-TAZ (4 g-0.5 g) was intravenously administered to 10 patients before abdominal surgery for inflammatory bowel disease. Blood, peritoneal fluid, and peritoneum samples were obtained at the end of infusion (0...
July 7, 2017: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28690028/meropenem-versus-piperacillin-tazobactam-with-or-without-immunoglobulin-as-second-line-therapy-for-febrile-neutropenia%C3%A2-in-pediatric-patients
#8
Ryoji Kobayashi, Daiki Hori, Hirozumi Sano, Daisuke Suzuki, Kenji Kishimoto, Kunihiko Kobayashi
BACKGROUND: Although survival of children with hematological diseases and cancer has increased dramatically, life-threatening complications due to bacterial infections occur in 5-10% of febrile episodes in pediatric cancer patients. A prospective randomized study was performed to clarify the usefulness of meropenem (MEPM) and piperacillin/tazobactam (PIPC/TAZ) with or without intravenous immunoglobulin (IVIG) as second-line therapy for pediatric patients with febrile neutropenia (FN)...
June 29, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28687864/stressed-podocytes-mechanical-forces-sensors-signaling-and-response
#9
REVIEW
Karlhans Endlich, Felix Kliewe, Nicole Endlich
Increased glomerular capillary pressure (glomerular hypertension) and increased glomerular filtration rate (glomerular hyperfiltration) have been proven to cause glomerulosclerosis in animal models and are likely to be operative in patients. Since podocytes cover the glomerular basement membrane, they are exposed to tensile stress due to circumferential wall tension and to fluid shear stress arising from filtrate flow through the narrow filtration slits and through Bowman's space. In vitro evidence documents that podocytes respond to tensile stress as well as to fluid shear stress...
July 7, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28677804/mapk-and-hippo-signaling-pathways-crosstalk-via-the-raf-1-mst-2-interaction-in-malignant-melanoma
#10
Ruizheng Feng, Junsheng Gong, Lina Wu, Lei Wang, Baolin Zhang, Gang Liang, Huixia Zheng, Hong Xiao
The aim of the present study was to expound on the interactions between the mitogen-activated protein kinase (MAPK) and Hippo pathway members, and to further elucidate the molecular mechanisms of melanoma tumorigenesis. Four melanoma cell lines (C32, HS695T, SK-MEL-28 and A375) were used in the present study. Western blotting was used to assess the expression levels of the MAPK and Hippo pathway effector proteins: rapidly accelerated fibrosarcoma-1 proto-oncogene, serine/threonine kinase (RAF-1); serine/threonine kinase 3 (STK3; also known as MST-2); yes-associated protein (YAP); and tafazzin (TAZ)...
June 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28671675/matrix-stiffness-induces-epithelial-mesenchymal-transition-and-promotes-chemoresistance-in-pancreatic-cancer-cells
#11
A J Rice, E Cortes, D Lachowski, B C H Cheung, S A Karim, J P Morton, A Del Río Hernández
Increased matrix rigidity associated with the fibrotic reaction is documented to stimulate intracellular signalling pathways that promote cancer cell survival and tumour growth. Pancreatic cancer is one of the stiffest of all human solid carcinomas and is characterised by a remarkable desmoplastic reaction. Here we use mouse models, genetically engineered to recapitulate human pancreatic cancer, and several pancreatic cancer cell lines as a model to investigate the effect of matrix stiffness in epithelial-mesenchymal transition (EMT) and resistance to chemotherapeutics...
July 3, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28668722/the-tyrosine-y250-2-39-in-frizzled-4-defines-a-conserved-motif-important-for-structural-integrity-of-the-receptor-and-recruitment-of-disheveled
#12
Katerina Strakova, Pierre Matricon, Chika Yokota, Elisa Arthofer, Ondrej Bernatik, David Rodriguez, Ernest Arenas, Jens Carlsson, Vitezslav Bryja, Gunnar Schulte
Frizzleds (FZDs) are unconventional G protein-coupled receptors, which activate diverse intracellular signaling pathways via the phosphoprotein Disheveled (DVL) and heterotrimeric G proteins. The interaction interplay of FZDs with DVL and G proteins is complex, involves different regions of FZD and the potential dynamics are poorly understood. In the present study, we aimed to characterize the function of a highly conserved tyrosine (Y250(2.39)) in the intracellular loop 1 (IL1) of human FZD4. We have found Y250(2...
June 29, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28658571/triazine-based-polyelectrolyte-as-an-efficient-cathode-interfacial-material-for-polymer-solar-cells
#13
Nallan Chakravarthi, Um Kanta Aryal, Kumarasamy Gunasekar, Ho-Yeol Park, Yeong-Soon Gal, Young-Rae Cho, Seong Il Yoo, Myungkwan Song, Sung-Ho Jin
A novel polyelectrolyte containing triazine (TAZ) and benzodithiophene (BDT) scaffolds with polar phosphine oxide (P═O) and quaternary ammonium ions as pendant groups, respectively, in the polymer backbone (PBTAZPOBr) was synthesized to use it as a cathode interfacial layer (CIL) for polymer solar cell (PSC) application. Owing to the high electron affinity of the TAZ unit and P═O group, PBTAZPOBr could behave as an effective electron transport material. Due to the polar quaternary ammonium and P═O groups, the interfacial dipole moment created by PBTAZPOBr substantially reduced the work function of the metal cathode to afford better energy alignment in the device, thus enabling electron extraction and reducing recombination of excitons at the photoactive layer/cathode interface...
July 11, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28647773/cthrc1-promotes-osteogenic-differentiation-of-periodontal-ligament-stem-cells-by-regulating-taz
#14
Chengze Wang, Weiting Gu, Baiyu Sun, Yunpeng Zhang, Yawen Ji, Xin Xu, Yong Wen
Collagen triple helix repeat containing 1 (CTHRC1) is associated with bone metabolism. Alveolar bone has an ability to rapidly remodel itself to adapt its biomechanical environment and function. However, whether CTHRC1 is expressed in alveolar bone tissue and the role of CTHRC1 in alveolar bone remodeling remain unclear. We used orthodontic tooth movement (OTM) rat model to study the effects of CHTRC1 in alveolar bone remodeling in vivo. We found that CTHRC1 was expressed in normal physiological condition of osteocytes, bone matrix, and periodontal ligament cells in rat...
August 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/28644436/the-lats1-and-lats2-tumor-suppressors-beyond-the-hippo-pathway
#15
REVIEW
Noa Furth, Yael Aylon
Proper cellular functionality and homeostasis are maintained by the convergent integration of various signaling cascades, which enable cells to respond to internal and external changes. The Dbf2-related kinases LATS1 and LATS2 (LATS) have emerged as central regulators of cell fate, by modulating the functions of numerous oncogenic or tumor suppressive effectors, including the canonical Hippo effectors YAP/TAZ, the Aurora mitotic kinase family, estrogen signaling and the tumor suppressive transcription factor p53...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28642262/arterial-stiffness-induces-remodeling-phenotypes-in-pulmonary-artery-smooth-muscle-cells-via-yap-taz-mediated-repression-of-cyclooxygenase-2
#16
Paul B Dieffenbach, Christina Mallarino Haeger, Anna Maria F Coronata, Kyoung Moo Choi, Xaralabos Varelas, Daniel J Tschumperlin, Laura E Fredenburgh
Pulmonary arterial stiffness is an independent risk factor for mortality in pulmonary hypertension (PH), and plays a critical role in PH pathophysiology. We have recently demonstrated arterial stiffening early in experimental PH, along with evidence for a mechanobiologic feedback loop by which arterial stiffening promotes further cellular remodeling behaviors. Cyclooxygenase-2 (COX-2) and prostaglandin signaling have been implicated in stiffness-mediated regulation, with prostaglandin activity inversely correlated to matrix stiffness and remodeling behaviors in vitro, as well as to disease progression in rodent PH models...
June 22, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28634072/mitochondrial-dynamics-coordinate-cell-differentiation
#17
Masafumi Noguchi, Atsuko Kasahara
Cells differentiate into specific and functional lineages to build up tissues. It has been shown in several tissues that mitochondrial morphology, levels of "mitochondrial shaping" proteins, and mitochondrial functions change upon differentiation. In this review, we highlight the significance of mitochondrial dynamics and functions in tissue development, cell differentiation, and reprogramming processes. Signalling cascades are critical for tissue stem cell maintenance and cell fate determination, and growing evidence demonstrates mitochondria could act as a centre of intra and extracellular signals to coordinate signalling pathways, such as Notch, Wnt, and YAP/TAZ signalling...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28634071/the-novel-yap-target-gene-sgk1-upregulates-taz-activity-by-blocking-gsk3%C3%AE-mediated-taz-destabilization
#18
Geon Yoo, Tackhoon Kim, Chaeuk Chung, Deog-Su Hwang, Dae-Sik Lim
YAP (Yes-associated protein) and TAZ (transcription activator with PDZ binding motif) are important in tissue regeneration and cancer development, highlighting the importance of discovering partners that regulate their oncogenicity. SGK1 (serum/glucocorticoid regulated kinase 1), initially identified as a homolog of Akt in phosphoinositide 3-kinase signaling, acts as a serine/threonine protein kinase in multiple oncogenic pathways. However, possible links between SGK1 and Hippo-YAP/TAZ signaling remain unexplored...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28628115/stearoyl-coa-desaturase-1-regulates-lung-cancer-stemness-via-stabilization-and-nuclear-localization-of-yap-taz
#19
A Noto, C De Vitis, M E Pisanu, G Roscilli, G Ricci, A Catizone, G Sorrentino, G Chianese, O Taglialatela-Scafati, D Trisciuoglio, D Del Bufalo, M Di Martile, A Di Napoli, L Ruco, S Costantini, Z Jakopin, A Budillon, G Melino, G Del Sal, G Ciliberto, R Mancini
This corrects the article DOI: 10.1038/onc.2017.75.
June 19, 2017: Oncogene
https://www.readbyqxmd.com/read/28620202/nanotopological-plate-stimulates-osteogenic-differentiation-through-taz-activation
#20
Jun-Ha Hwang, Dong-Hyun Lee, Mi Ran Byun, A Rum Kim, Kyung Min Kim, Jung Il Park, Ho Taek Oh, Eun Sook Hwang, Kyu Back Lee, Jeong-Ho Hong
The topographical environment, which mimics the stem cell niche, provides mechanical cues to regulate the differentiation of mesenchymal stem cells (MSC). Diverse topographical variations have been engineered to investigate cellular responses; however, the types of mechanical parameters that affect cells, and their underlying mechanisms remain largely unknown. In this study, we screened nanotopological pillars with size gradient to activate transcriptional coactivator with PDZ binding motif (TAZ), which stimulates osteogenesis of MSC...
June 15, 2017: Scientific Reports
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