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https://www.readbyqxmd.com/read/28438716/yap1-negatively-regulates-chondrocyte-differentiation-partly-by-activating-the-%C3%AE-catenin-signaling-pathway
#1
Beining Yang, Hualing Sun, Fangfang Song, Miao Yu, Yanru Wu, Jiawei Wang
YAP1 (Yes-associated protein 1) transcriptional coactivator is a downstream gene of the Hippo signaling pathway, which controls cell proliferation and differentiation. YAP1 plays a significant role in the regulation of cartilage and bone development. However, the molecular mechanism by which YAP1 regulates chondrocyte differentiation remains to be elucidated. Immunofluorescent staining was used to visualize the localization of YAP1 expression in the mouse chondroprogenitor ATDC5 cell line. ATDC5 cells with lentivirus-vector-mediated YAP1 overexpression and knockdown were established...
April 21, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28435452/the-yap1-six2-axis-is-required-for-ddx3-mediated-tumor-aggressiveness-and-cetuximab-resistance-in-kras-wild-type-colorectal-cancer
#2
De-Wei Wu, Po-Lin Lin, Lee Wang, Chi-Chou Huang, Huei Lee
The mechanism underlying tumor aggressiveness and cetuximab (CTX) resistance in KRAS-wild-type (KRAS -WT) colorectal cancer remains obscure. We here provide evidence that DDX3 promoted soft agar growth and invasiveness of KRAS-WT cells, as already confirmed in KRAS-mutated cells. Mechanistically, increased KRAS expression induced ROS production, which elevated HIF-1α and YAP1 expression. Increased HIF-1α persistently promoted DDX3 expression via a KRAS/ROS/HIF-1α feedback loop. DDX3-mediated aggressiveness and CTX resistance were regulated by the YAP1/SIX2 axis in KRAS-WT cells and further confirmed in animal models...
2017: Theranostics
https://www.readbyqxmd.com/read/28433598/mir-590-5p-a-density-sensitive-microrna-inhibits-tumorigenesis-by-targeting-yap1-in-colorectal-cancer
#3
Chunlin Ou, Zhenqiang Sun, Xiayu Li, Xiaoling Li, Weiguo Ren, Zailong Qin, Xuemei Zhang, Weitang Yuan, Jia Wang, Wentao Yu, Shiwen Zhang, Qiu Peng, Qun Yan, Wei Xiong, Guiyuan Li, Jian Ma
YAP1, a transcription co-activator, mediates the biological functions of the Hippo pathway. YAP1 inactivation is involved in cell-cell contact inhibition. In various tumors, YAP1 is upregulated through multiple mechanisms, and it functions as an oncogene. Here, we provided evidence that YAP1 influenced multiple signaling pathways in colorectal cancer (CRC) cells. We reported that miR-590-5p directly targets YAP1 and inhibits tumorigenesis in CRC cells both in vitro and in vivo xenograft model. We analyzed different cell densities and found that increased density caused increased expression of miR-590-5p, and decreased expression of its precursors (pri- and pre-miR-590)...
April 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28427825/molecular-mechanisms-of-the-yeast-adaptive-response-and-tolerance-to-stresses-encountered-during-ethanol-fermentation
#4
REVIEW
Choowong Auesukaree
During ethanol fermentation, yeast cells encounter various stresses including sugar substrates-induced high osmolarity, increased ethanol concentration, oxygen metabolism-derived reactive oxygen species (ROS), and elevated temperature. To cope with these fermentation-associated stresses, appropriate adaptive responses are required to prevent stress-induced cellular dysfunctions and to acquire stress tolerances. This review will focus on the cellular effects of these stresses, molecular basis of the adaptive response to each stress, and the cellular mechanisms contributing to stress tolerance...
April 17, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28424666/napa-mediates-a-redox-regulation-of-the-antioxidant-response-carbon-utilization-and-development-in-aspergillus-nidulans
#5
Ariann E Mendoza-Martínez, Fernando Lara-Rojas, Olivia Sánchez, Jesús Aguirre
The redox-regulated transcription factors (TFs) of the bZIP AP1 family, such as yeast Yap1 and fission yeast Pap1, are activated by peroxiredoxin proteins (Prxs) to regulate the antioxidant response. Previously, Aspergillus nidulans mutants lacking the Yap1 ortholog NapA have been characterized as sensitive to H2O2 and menadione. Here we study NapA roles in relation to TFs SrrA and AtfA, also involved in oxidant detoxification, showing that these TFs play different roles in oxidative stress resistance, catalase gene regulation and development, during A...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28418643/diphenyl-diselenide-protects-against-methylmercury-induced-toxicity-in-saccharomyces-cerevisiae-via-the-yap1-transcription-factor
#6
Fabricio Luís Lovato, João B T Rocha, Cristiane Lenz Dalla Corte
Methylmercury (MeHg) is a ubiquitous and persistent environmental pollutant that induces serious neurotoxic effects. Diphenyl diselenide [(PhSe)2], an organoseleno-compound, exerts protective effects against MeHg toxicity, although the complete mechanism remains unclear. The aim of this study was to investigate the mechanisms involved in the protective effect of (PhSe)2 on the toxicity induced by MeHg using wild-type Saccharomyces cerevisiae and mutants with defects in enzymes and proteins of the antioxidant defense system (yap1Δ, ybp1Δ, ctt1Δ, cat1Δ, sod1Δ, sod2Δ, gsh1Δ, gsh2Δ, gtt1Δ, gtt2Δ, gtt3Δ, gpx1Δ, gpx2Δ, trx1Δ, trx2Δ, trx3Δ and trr2Δ)...
April 18, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28381547/eif5a-peak1-signaling-regulates-yap1-taz-protein-expression-and-pancreatic-cancer-cell-growth
#7
Jan Strnadel, Sunkyu Choi, Ken Fujimura, Huawei Wang, Wei Zhang, Meghan Wyse, Tracy Wright, Emilie Gross, Carlos Peinado, Hyun Woo Park, Jack Bui, Jonathan Kelber, Michael Bouvet, Kun-Liang Guan, Richard L Klemke
In pancreatic ductal adenocarcinoma (PDAC), mutant KRAS stimulates the translation initiation factor eIF5A and upregulates the focal adhesion kinase PEAK1, which transmits integrin and growth factor signals mediated by the tumor microenvironment. Although eIF5A-PEAK1 signaling contributes to multiple aggressive cancer cell phenotypes, the downstream signaling processes that mediate these responses are uncharacterized. Through proteomics and informatic analyses of PEAK1-depleted PDAC cells, we defined protein translation, cytoskeleton organization, and cell-cycle regulatory pathways as major pathways controlled by PEAK1...
April 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28381174/distinct-prognostic-values-of-yap1-in-gastric-cancer
#8
Lan Yu, Chun Gao, Bei Feng, Liming Wang, Xun Tian, Hui Wang, Ding Ma
The Hippo pathway regulates intrinsic organ sizes by regulating apoptosis and cell proliferation. YAP1 (yes-associated protein 1) is a transcriptional effector of the Hippo pathway. YAP1 expression is reported to be associated with gastric cancer carcinogenesis and malignancy. In this study, we compared the expression of YAP1 in gastric cancer and normal stomach tissues. Tissue microarray analysis was performed in 156 gastric cancer samples, 8 adjacent normal stomach tissues, and 4 normal stomach tissues. We also analyzed the association between YAP1 protein expression and clinicopathological features, such as age, gender, histological differentiation, and clinical stages...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28376174/role-of-yap1-as-a-marker-of-sensitivity-to-dual-akt-and-p70s6k-inhibition-in-ovarian-and-uterine-malignancies
#9
Rebecca A Previs, Guillermo N Armaiz-Pena, Cristina Ivan, Heather J Dalton, Rajesha Rupaimoole, Jean M Hansen, Yasmin Lyons, Jie Huang, Monika Haemmerle, Michael J Wagner, Kshipra M Gharpure, Archana S Nagaraja, Justyna Filant, Michael H McGuire, Kyunghee Noh, Piotr L Dorniak, Sarah L Linesch, Lingegowda S Mangala, Sunila Pradeep, Sherry Y Wu, Anil K Sood
Background: The PI3K/AKT/P70S6K pathway is an attractive therapeutic target in ovarian and uterine malignancies because of its high rate of deregulation and key roles in tumor growth. Here, we examined the biological effects of MSC2363318A, which is a novel inhibitor of AKT1, AKT3, and P70S6K. Methods: Orthotopic murine models of ovarian and uterine cancer were utilized to study the effect of MSC2363318A on survival and regression. For each cell line, 10 mice were treated in each of the experimental arms tested...
July 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28376152/co-activation-of-stat3-and-yes-associated-protein-1-yap1-pathway-in-egfr-mutant-nsclc
#10
Imane Chaib, Niki Karachaliou, Sara Pilotto, Jordi Codony Servat, Xueting Cai, Xuefei Li, Ana Drozdowskyj, Carles Codony Servat, Jie Yang, Chunping Hu, Andres Felipe Cardona, Guillermo Lopez Vivanco, Alain Vergnenegre, Jose Miguel Sanchez, Mariano Provencio, Noemi Reguart, Caicun Zhou, Peng Cao, Patrick C Ma, Trever G Bivona, Rafael Rosell
Background: The efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC) is limited by adaptive activation of cell survival signals. We hypothesized that both signal transducer and activator of transcription 3 (STAT3) and Src-YES-associated protein 1 (YAP1) signaling are dually activated during EGFR TKI treatment to limit therapeutic response. Methods: We used MTT and clonogenic assays, immunoblotting, and quantitative polymerase chain reaction to evaluate the efficacy of EGFR TKI alone and in combination with STAT3 and Src inhibition in three EGFR-mutant NSCLC cell lines...
September 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28373298/mob1-mediated-phospho-recognition-in-the-core-mammalian-hippo-pathway
#11
Amber L Couzens, Shawn Xiong, James Dr Knight, Daniel Y Mao, Sebastian Guettler, Sarah Picaud, Igor Kurinov, Panagis Filippakopoulos, Frank Sicheri, Anne-Claude Gingras
The Hippo tumor suppressor pathway regulates organ size and tissue homoeostasis in response to diverse signaling inputs. The core of the pathway consists of a short kinase cascade: MST1 and MST2 phosphorylate and activate LATS1 and LATS2, which in turn phosphorylate and inactivate key transcriptional co-activators, YAP1 and TAZ (gene WWTR1). The MOB1 adapter protein regulates both phosphorylation reactions firstly by concurrently binding to the upstream MST and downstream LATS kinases to enable the trans phosphorylation reaction, and secondly by allosterically activating the catalytic function of LATS1 and LATS2 to directly stimulate phosphorylation of YAP and TAZ...
April 3, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28363815/proteomic-profiling-of-isogenic-primary-and-metastatic-medulloblastoma-cell-lines-reveals-differential-expression-of-key-metastatic-factors
#12
Shuo Gu, Kai Chen, Minzhi Yin, Zhixiang Wu, Yeming Wu
Medulloblastoma is the most common malignant brain tumor in children. Around 30% of medulloblastoma patients are diagnosed with metastasis, which often results in a poor prognosis. Unfortunately, molecular mechanisms of medulloblastoma metastasis remain largely unknown. In this study, we employed the recently developed deep proteome analysis approach to quantitatively profile the expression of >10,000 proteins from CHLA-01-MED and CHLA-01R-MED isogenic cell lines derived from the primary and metastatic tumor of the same patient diagnosed with a group IV medulloblastoma...
March 28, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28361556/fungicide-xylaria-sp-bcc-1067-extract-induces-reactive-oxygen-species-and-activates-multidrug-resistance-system-in-saccharomyces-cerevisiae
#13
Pichayada Somboon, Attaporn Poonsawad, Songsak Wattanachaisaereekul, Laran T Jensen, Masakazu Niimi, Supapon Cheevadhanarak, Nitnipa Soontorngun
AIM: To investigate antifungal potential of Xylaria sp. BIOTEC culture collection (BCC) 1067 extract against the model yeast Saccharomyces cerevisiae. MATERIALS & METHODS: Antifungal property of extract, reactive oxygen species levels and cell survival were determined, using selected deletion strains. RESULTS: Extract showed promising antifungal effect with minimal inhibitory concentration100 and minimal fungicidal concentration of 500 and 1000 mg/l, respectively...
April 2017: Future Microbiology
https://www.readbyqxmd.com/read/28356122/integrated-analysis-identifies-microrna-195-as-a-suppressor-of-hippo-yap-pathway-in-colorectal-cancer
#14
Min Sun, Haibin Song, Shuyi Wang, Chunxiao Zhang, Liang Zheng, Fangfang Chen, Dongdong Shi, Yuanyuan Chen, Chaogang Yang, Zhenxian Xiang, Qing Liu, Chen Wei, Bin Xiong
BACKGROUND: With persistent inconsistencies in colorectal cancer (CRC) miRNAs expression data, it is crucial to shift toward inclusion of a "pre-laboratory" integrated analysis to expedite effective precision medicine and translational research. Aberrant expression of hsa-miRNA-195 (miR-195) which is distinguished as a clinically noteworthy miRNA has previously been observed in multiple cancers, yet its role in CRC remains unclear. METHODS: In this study, we performed an integrated analysis of seven CRC miRNAs expression datasets...
March 29, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28350986/flow-dependent-endothelial-yap-regulation-contributes-to-vessel-maintenance
#15
Hiroyuki Nakajima, Kimiko Yamamoto, Sobhika Agarwala, Kenta Terai, Hajime Fukui, Shigetomo Fukuhara, Koji Ando, Takahiro Miyazaki, Yasuhiro Yokota, Etienne Schmelzer, Heinz-Georg Belting, Markus Affolter, Virginie Lecaudey, Naoki Mochizuki
Endothelial cells (ECs) line the inside of blood vessels and respond to mechanical cues generated by blood flow. Mechanical stimuli regulate the localization of YAP by reorganizing the actin cytoskeleton. Here we demonstrate blood-flow-mediated regulation of endothelial YAP in vivo. We indirectly monitored transcriptional activity of Yap1 (zebrafish YAP) and its spatiotemporal localization in living zebrafish and found that Yap1 entered the nucleus and promoted transcription in response to blood flow. In cultured human ECs, laminar shear stress induced nuclear import of YAP and its transcriptional activity in a manner independent of Hippo signaling...
March 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28346423/mob1-yap1-taz-nkx2-1-axis-controls-bronchioalveolar-cell-differentiation-adhesion-and-tumour-formation
#16
K Otsubo, H Goto, M Nishio, K Kawamura, S Yanagi, W Nishie, T Sasaki, T Maehama, H Nishina, K Mimori, T Nakano, H Shimizu, T W Mak, K Nakao, Y Nakanishi, A Suzuki
Mps One Binder Kinase Activator (MOB)1A/1B are core components of the Hippo pathway. These proteins, which coactivate LArge Tumour Suppressor homologue kinases, are also tumour suppressors. To investigate MOB1A/B's roles in normal physiology and lung cancer, we generated doxycycline (Dox)-inducible, bronchioalveolar epithelium-specific, null mutations of MOB1A/B in mice (SPC-rtTA/(tetO)7-Cre/Mob1a(flox/flox)/Mob1b(-/-); termed luMob1DKO mice). Most mutants (70%) receiving Dox in utero (luMob1DKO (E6.5-18.5) mice) died of hypoxia within 1 h post-birth...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28339095/expression-of-yes-associated-protein%C3%A2-1-and-its-clinical-significance-in-ovarian-serous-cystadenocarcinoma
#17
Sang Yeon Cho, Kwanghun Kim, Min Soo Park, Mi Young Jang, Young Hwan Choi, Suyeon Han, Hyun Mo Shin, Chaeuk Chung, Hye Young Han, Jung Bo Yang, Young Bok Ko, Heon Jong Yoo
Yes-associated protein 1 (YAP1) is a key transcriptional regulator in the Hippo signaling pathway that plays a critical role in the development and progression of several types of malignancies, including ovarian cancer. Herein, we investigated the expression of YAP1 and its clinical significance in a large population of patients with ovarian serous cystadenocarcinoma (OSC), which is the most common form of epithelial ovarian neoplasm, using the TCGA database. Surprisingly, cross-cancer mRNA expression and alterations in YAP1 were higher in OSC than in those of other types of cancers in the TCGA database...
March 21, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28325852/extended-multiplexing-of-tmt-labeling-reveals-age-and-high-fat-diet-specific-proteome-changes-in-mouse-epididymal-adipose-tissue
#18
Deanna L Plubell, Phillip A Wilmarth, Yuqi Zhao, Alexandra M Fenton, Jessica Minnier, Ashok P Reddy, John Klimek, Xia Yang, Larry L David, Nathalie Pamir
The lack of high-throughput methods to analyze the adipose tissue protein composition limits our understanding of the protein networks responsible for age and diet related metabolic response. We have developed an approach using multiple-dimension liquid chromatography tandem mass spectrometry and extended multiplexing (24 biological samples) with TMT labeling to analyze proteomes of epididymal adipose tissues isolated from mice fed either low or high fat diet for a short or a long-term, and from mice that aged on low vs...
March 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28315521/systematic-morphological-profiling-of-human-gene-and-allele-function-via-cell-painting
#19
Mohammad Hossein Rohban, Shantanu Singh, Xiaoyun Wu, Julia B Berthet, Mark-Anthony Bray, Yashaswi Shrestha, Xaralabos Varelas, Jesse S Boehm, Anne E Carpenter
We hypothesized that human genes and disease-associated alleles might be systematically functionally annotated using morphological profiling of cDNA constructs, via a microscopy-based Cell Painting assay. Indeed, 50% of the 220 tested genes yielded detectable morphological profiles, which grouped into biologically meaningful gene clusters consistent with known functional annotation (e.g., the RAS-RAF-MEK-ERK cascade). We used novel subpopulation-based visualization methods to interpret the morphological changes for specific clusters...
March 18, 2017: ELife
https://www.readbyqxmd.com/read/28293931/investigation-of-the-possible-role-of-the-hippo-yap1-pathway-in-asthma-and-allergy
#20
Lili E Fodor, András Gézsi, Ldikó Ungvári, Agnes F Semsei, Zsófia Gál, Adrienne Nagy, Gabriella Gálffy, Lilla Tamási, András Kiss, Péter Antal, Csaba Szalai
PURPOSE: Several lines of evidence indicate that the Hippo/Yes-associated protein 1 (YAP1) pathways might play a role in the pathogenesis of asthma. To investigate the possible role of the Hippo/YAP1 pathway in the pathogenesis of asthma or its phenotypes. METHODS: The levels of gene expressions of the members of the Hippo/YAP1 were compared. The presence of the proteins of the YAP1 and FRMD6 were analyzed with Western blot in induced sputum of 18 asthmatic subjects and 10 control subjects...
May 2017: Allergy, Asthma & Immunology Research
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