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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
#1
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
#2
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
#3
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
https://www.readbyqxmd.com/read/28274310/-mir-590-5p-inhibits-a375-cell-invasion-and-migration-in-malignant-melanoma-by-directly-inhibiting-yap1-expression
#4
Lijuan Wang, Shengjia Shi, Yan Zhou, Xin Mu, Dan Han, Rui Ge, Kuanhou Mu
Objective To detect the expression of miR-590-5p in malignant melanoma A375 cells, its effect on the invasion and migration of A375 cells, and underlying mechanism. Methods Real-time PCR was performed to detect the expression of miR-590-5p in A375 cells and human normal melanocyte (HM) cells; Transwell(TM) assay and wound healing assay were used to observe the effect of miR-590-5p on the invasion and migration of A375 cells; Luciferase assay was done to determine whether YAP1 was the direct target of miR-590-5p; quantitative real-time PCR and Western blotting were performed to investigate the effect of miR-590-5p on YAP1 expression...
March 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28262546/promotion-effects-of-mir-375-on-the-osteogenic-differentiation-of-human-adipose-derived-mesenchymal-stem-cells
#5
Si Chen, Yunfei Zheng, Shan Zhang, Lingfei Jia, Yongsheng Zhou
MicroRNA plays an important role in bone tissue engineering; however, its role and function in osteogenic differentiation warrant further investigation. In this study, we demonstrated that miR-375 was upregulated during the osteogenic differentiation of human adipose-derived mesenchymal stem cells (hASCs). Overexpression of miR-375 significantly enhanced hASCs osteogenesis both in vitro and in vivo, while knockdown of miR-375 inhibited the osteogenic differentiation of hASCs. Mechanistically, microarray analysis revealed DEPTOR as a target of miR-375 in hASCs...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28253715/microrna-1285-inhibits-malignant-biological-behaviors-of-human-pancreatic-cancer-cells-by-negative-regulation-of-yap1
#6
H Huang, G Xiong, P Shen, Z Cao, L Zheng, T Zhang, Y Zhao
Pancreatic ductal adenocarcinoma is a most deadly malignancy, with a 5-year survival rate of ~7%. Chemotherapy is the main treatment strategy of this disease. However, the high rate of resistance to chemotherapeutic agent contributes to poor prognosis. MicroRNAs are essential for the initiation, progression and chemoresistance of human malignancies. Previous studies have shown that miRNA-1285 participates in renal cell carcinoma and hepatocellular carcinoma. However, its roles in pancreatic ductal adenocarcinoma are poorly understood...
March 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/28249813/induction-of-chromosome-instability-by-activation-of-yes-associated-protein-and-forkhead-box-m1-in-liver-cancer
#7
Sofia M E Weiler, Federico Pinna, Thomas Wolf, Teresa Lutz, Aman Geldiyev, Carsten Sticht, Maria Knaub, Stefan Thomann, Michaela Bissinger, Shan Wan, Stephanie Rössler, Diana Becker, Norbert Gretz, Hauke Lang, Frank Bergmann, Vladimir Ustiyan, Tatiana V Kalin, Stephan Singer, Ju-Seog Lee, Jens U Marquardt, Peter Schirmacher, Vladimir V Kalinichenko, Kai Breuhahn
BACKGROUND & AIMS: Many different types of cancer cells have chromosome instability. The hippo pathway leads to phosphorylation of the transcriptional activator yes associated protein 1 (YAP1, YAP), which regulates proliferation and has been associated with development of liver cancer. We investigated the effects of hippo signaling via YAP on chromosome stability and hepatocarcinogenesis in humans and mice. METHODS: We analyzed transcriptome data from 242 patients with hepatocellular carcinoma (HCC) to search for gene signatures associated with chromosomal instability; we investigated associations with overall survival time and cancer recurrence using Kaplan-Meier curves...
February 26, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28245913/a-new-view-of-pathway-driven-drug-resistance-in-tumor-proliferation
#8
REVIEW
Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang
Defeating drug resistance in tumor cell proliferation is challenging. We propose that signaling in cell proliferation takes place via two core pathways, each embodying multiple alternative pathways. We consider drug resistance through an alternative proliferation pathway - within the same or within the other core pathway. Most drug combinations target only one core pathway; blocking both can restrain proliferation. We define core pathways as independent and acting similarly in cell-cycle control, which can explain why their products (e...
February 25, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28245464/the-hippo-signaling-pathway-regulates-ovarian-function-via-the-proliferation-of-ovarian-germline-stem-cells
#9
Haifeng Ye, Xiaoyan Li, Tuochen Zheng, Chuan Hu, Zezheng Pan, Jian Huang, Jia Li, Wei Li, Yuehui Zheng
OBJECTIVE: To improve the separation, identification and cultivation of ovarian germline stem cells (OGSCs), to clarify the relationship between the Hippo signaling pathway effector YAP1 and the proliferation and differentiation of OGSCs in vitro and to identify the major contribution of Hippo signaling to ovarian function. METHODS: Two-step enzymatic separation processes and magnetic separation were used to isolate and identify OGSCs by determining the expression of Mvh, Oct4, Nanog, Fragilis and Stella markers...
February 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28241877/ovatodiolide-suppresses-colon-tumorigenesis-and-prevents-polarization-of-m2-tumor-associated-macrophages-through-yap-oncogenic-pathways
#10
Yan-Jiun Huang, Ching-Kuo Yang, Po-Li Wei, Thanh-Tuan Huynh, Jacqueline Whang-Peng, Tzu-Ching Meng, Michael Hsiao, Yew-Ming Tzeng, Alexander Th Wu, Yun Yen
BACKGROUND: An increased expression of Yes-associated protein (YAP1) has been shown to promote tumorigenesis in many cancer types including colon. However, the role of YAP1 in promoting colon tumorigenesis remains unclear. Here, we demonstrate that YAP1 expression is associated with M2 tumor-associated macrophage polarization and the generation of colon cancer stem-like cells. YAP1 downregulation by gene silencing or a phytochemical, ovatodiolide, not only suppresses colon cancer tumorigenesis but also prevents M2 TAM polarization...
February 28, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28239148/amotl1-mediates-sequestration-of-the-hippo-effector-yap1-downstream-of-fat4-to-restrict-heart-growth
#11
Chiara V Ragni, Nicolas Diguet, Jean-François Le Garrec, Marta Novotova, Tatiana P Resende, Sorin Pop, Nicolas Charon, Laurent Guillemot, Lisa Kitasato, Caroline Badouel, Alexandre Dufour, Jean-Christophe Olivo-Marin, Alain Trouvé, Helen McNeill, Sigolène M Meilhac
Although in flies the atypical cadherin Fat is an upstream regulator of Hippo signalling, the closest mammalian homologue, Fat4, has been shown to regulate tissue polarity rather than growth. Here we show in the mouse heart that Fat4 modulates Hippo signalling to restrict growth. Fat4 mutant myocardium is thicker, with increased cardiomyocyte size and proliferation, and this is mediated by an upregulation of the transcriptional activity of Yap1, an effector of the Hippo pathway. Fat4 is not required for the canonical activation of Hippo kinases but it sequesters a partner of Yap1, Amotl1, out of the nucleus...
February 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28231263/uniformity-under-in-vitro-conditions-changes-in-the-phenotype-of-cancer-cell-lines-derived-from-different-medulloblastoma-subgroups
#12
Petr Chlapek, Karel Zitterbart, Leos Kren, Lenka Filipova, Jaroslav Sterba, Renata Veselska
Medulloblastoma comprises four main subgroups (WNT, SHH, Group 3 and Group 4) originally defined by transcriptional profiling. In primary medulloblastoma tissues, these groups are thought to be distinguishable using the immunohistochemical detection of β-catenin, filamin A, GAB1 and YAP1 protein markers. To investigate the utility of these markers for in vitro studies using medulloblastoma cell lines, immunoblotting and indirect immunofluorescence were employed for the detection of β-catenin, filamin A, GAB1 and YAP1 in both DAOY and D283 Med reference cell lines and the panel of six medulloblastoma cell lines derived in our laboratory from the primary tumor tissues of known molecular subgroups...
2017: PloS One
https://www.readbyqxmd.com/read/28222762/the-hippo-component-yap-localizes-in-the-nucleus-of-human-papilloma-virus-positive-oropharyngeal-squamous-cell-carcinoma
#13
Faisal Alzahrani, Leanne Clattenburg, Shanmugam Muruganandan, Martin Bullock, Kaitlyn MacIsaac, Michael Wigerius, Blair A Williams, M Elise R Graham, Matthew H Rigby, Jonathan R B Trites, S Mark Taylor, Christopher J Sinal, James P Fawcett, Robert D Hart
BACKGROUND: HPV infection causes cervical cancer, mediated in part by the degradation of Scribble via the HPV E6 oncoprotein. Recently, Scribble has been shown to be an important regulator of the Hippo signaling cascade. Deregulation of the Hippo pathway induces an abnormal cellular transformation, epithelial to mesenchymal transition, which promotes oncogenic progression. Given the recent rise in oropharyngeal HPV squamous cell carcinoma we sought to determine if Hippo signaling components are implicated in oropharyngeal squamous cell carcinoma...
February 22, 2017: Journal of Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/28219524/the-function-and-transcriptome-analysis-of-a-bzip-transcription-factor-cgap1-in-colletotrichum-gloeosporioides
#14
Xiaoyu Li, Yateng Wu, Zhiqiang Liu, Chenghui Zhang
Colletotrichum gloeosporioides is an important pathogen of anthracnose, which is able to infect numerous crops in tropical and subtropical regions, causing great economic losses. To investigate the fungal response to host-generated reactive oxygen species (ROS), we cloned and characterized the CgAP1 gene of C. gloeosporioides. CgAP1 encoded a bZIP transcription factor which had a bZIP DNA-binding domain and two cysteine-rich domains structurally and functionally related to Saccharomyces cerevisiae YAP1. Deletion of CgAP1 in C...
April 2017: Microbiological Research
https://www.readbyqxmd.com/read/28212550/plcb4-copy-gain-and-plc%C3%A3-4-overexpression-in-primary-gastrointestinal-stromal-tumors-integrative-characterization-of-a-lipid-catabolizing-enzyme-associated-with-worse-disease-free-survival
#15
Chien-Feng Li, Ting-Ting Liu, I-Chieh Chuang, Yen-Yang Chen, Fu-Min Fang, Ti-Chun Chan, Wan-Shan Li, Hsuan-Ying Huang
To explore the implications of lipid catabolism-associated genes in gastrointestinal stromal tumors, we reappraised transcriptomic and genomic datasets and identified copy-gained and differentially upregulated PLCB4 gene associated with tumor progression. On full sections, PLCB4 mRNA abundance and PLCß4 immunoexpression were validated in 70 cases. On tissue microarrays, PLCB4 gene copies and PLCß4 immunoexpression were both informative in 350 cases with KIT/PDGFRA/BRAF genotypes noted in 213. In GIST48 cell line, we stably silenced PLCB4 and YAP1 to characterize their functional effects and regulatory link...
February 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28195137/erbb4-confers-risk-for-polycystic-ovary-syndrome-in-han-chinese
#16
Yingqian Peng, Wei Zhang, Ping Yang, Ye Tian, Shizhen Su, Changming Zhang, Zi-Jiang Chen, Han Zhao
A recent genome-wide association study (GWAS) of polycystic ovary syndrome (PCOS) in European cohorts has identified six susceptibility loci mapping to 11q22.1 (YAP1), 2p21 (THADA), 11p14.1 (FSHB), 2q34 (ERBB4), 12q21.2 (KRR1), and 5q31.1 (RAD50). The loci of 11q22.1, 2p21 and 11p14.1 have been confirmed to be associated with PCOS in Chinese; whereas the other three new loci (2q34, 12q21.2, and 5q31.1) still need to be evaluated in Chinese. This study was aimed to determine if the three new loci identified in European PCOS also confer risks for PCOS in Han Chinese...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194015/induced-p53-loss-in-mouse-luminal-cells-causes-clonal-expansion-and-development-of-mammary-tumours
#17
Luwei Tao, Dongxi Xiang, Ying Xie, Roderick T Bronson, Zhe Li
Most breast cancers may have a luminal origin. TP53 is one of the most frequently mutated genes in breast cancers. However, how p53 deficiency contributes to breast tumorigenesis from luminal cells remains elusive. Here we report that induced p53 loss in Krt8(+) mammary luminal cells leads to their clonal expansion without directly affecting their luminal identity. All induced mice develop mammary tumours with 9qA1 (Yap1) and/or 6qA2 (Met) amplification(s). These tumours exhibit a mammary stem cell (MaSC)-like expression signature and most closely resemble claudin-low breast cancer...
February 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28182302/podoplanin-promotes-progression-of-malignant-pleural-mesothelioma-by-regulating-motility-and-focus-formation
#18
Shinji Takeuchi, Koji Fukuda, Tadaaki Yamada, Sachiko Arai, Satoshi Takagi, Gen-Ichiro Ishii, Atsushi Ochiai, Shotaro Iwakiri, Kazumi Itoi, Hisanori Uehara, Hiroshi Nishihara, Naoya Fujita, Seiji Yano
Malignant pleural mesothelioma (MPM) is characterized by dissemination and aggressive growth in the thoracic cavity. Podoplanin (PDPN) is an established diagnostic marker for MPM, but the function of PDPN in MPM is not fully understood. The purpose of this study was to determine the pathogenetic function of PDPN in MPM. Forty-seven of 52 tumors (90%) from Japanese patients with MPM and 3/6 (50%) MPM cell lines tested positive for PDPN. Knocking down PDPN in PDPN-high expressing MPM cells resulted in decreased cell motility...
February 9, 2017: Cancer Science
https://www.readbyqxmd.com/read/28123852/histone-demethylase-jmjd1c-regulates-esophageal-cancer-proliferation-via-yap1-signaling
#19
Yixin Cai, Xiangning Fu, Yu Deng
Esophageal cancer (EC) is the most lethal cancer, and it is of significant concern worldwide, particularly in China. However, there are no effective treatments to cure it, such as chemotherapy, surgery, or radiotherapy. This is attributed to the lack of understanding of the molecular mechanisms of EC. Recently, the superfamily of Jmj-containing KDMs has been shown to play an important role in tumorigenesis in various cancers, including EC. In this study, we demonstrated that JMJD1C was upregulated in patient EC tissues and different EC cell lines...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28098159/fluid-shear-stress-activates-yap1-to-promote-cancer-cell-motility
#20
Hyun Jung Lee, Miguel F Diaz, Katherine M Price, Joyce A Ozuna, Songlin Zhang, Eva M Sevick-Muraca, John P Hagan, Pamela L Wenzel
Mechanical stress is pervasive in egress routes of malignancy, yet the intrinsic effects of force on tumour cells remain poorly understood. Here, we demonstrate that frictional force characteristic of flow in the lymphatics stimulates YAP1 to drive cancer cell migration; whereas intensities of fluid wall shear stress (WSS) typical of venous or arterial flow inhibit taxis. YAP1, but not TAZ, is strictly required for WSS-enhanced cell movement, as blockade of YAP1, TEAD1-4 or the YAP1-TEAD interaction reduces cellular velocity to levels observed without flow...
January 18, 2017: Nature Communications
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