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https://www.readbyqxmd.com/read/28231263/uniformity-under-in-vitro-conditions-changes-in-the-phenotype-of-cancer-cell-lines-derived-from-different-medulloblastoma-subgroups
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/28087810/akt1-lkb1-and-yap1-revealed-as-myc-interactors-with-nanoluc-based-protein-fragment-complementation-assay
#10
Xiu-Lei Mo, Qi Qi, Andrei A Ivanov, Qiankun Niu, Yin Luo, Jonathan Havel, Russell Goetze, Sydney Bell, Carlos S Moreno, Lee A D Cooper, Margaret A Johns, Fadlo R Khuri, Yuhong Du, Haian Fu
The c-Myc (MYC) transcription factor is a major cancer driver and a well-validated therapeutic target. However, directly targeting MYC has been challenging. Thus, identifying proteins that interact with and regulate MYC may provide alternative strategies to inhibit its oncogenic activity. Here we report the development of a NanoLuc®-based protein-fragment complementation assay (NanoPCA) and mapping of the MYC protein interaction hub in live mammalian cells. The NanoPCA system was configured to enable detection of protein-protein interactions (PPI) at the endogenous level, as shown with PRAS40 dimerization, and detection of weak interactions, such as PINCH1-NCK2...
January 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28087714/dlg5-connects-cell-polarity-and-hippo-signaling-protein-networks-by-linking-par-1-with-mst1-2
#11
Julian Kwan, Anna Sczaniecka, Emad Heidary Arash, Liem Nguyen, Chia-Chun Chen, Srdjana Ratkovic, Olga Klezovitch, Liliana Attisano, Helen McNeill, Andrew Emili, Valeri Vasioukhin
Disruption of apical-basal polarity is implicated in developmental disorders and cancer; however, the mechanisms connecting cell polarity proteins with intracellular signaling pathways are largely unknown. We determined previously that membrane-associated guanylate kinase (MAGUK) protein discs large homolog 5 (DLG5) functions in cell polarity and regulates cellular proliferation and differentiation via undefined mechanisms. We report here that DLG5 functions as an evolutionarily conserved scaffold and negative regulator of Hippo signaling, which controls organ size through the modulation of cell proliferation and differentiation...
December 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/28079802/promoter-methylation-of-yes-associated-protein-yap1-gene-in-polycystic-ovary-syndrome
#12
Li-Le Jiang, Juan-Ke Xie, Jin-Quan Cui, Duo Wei, Bao-Li Yin, Ya-Nan Zhang, Yuan-Hui Chen, Xiao Han, Qian Wang, Cui-Lian Zhang
BACKGROUND: DNA methylation modification has been proved to influence the phenotype of polycystic ovary syndrome (PCOS). Genome-wide association studies (GWAS) demonstrate that yes-associated protein (YAP1) genetic sites are associated with PCOS. The study aims to detect the methylation status of YAP1 promoter in ovary granulosa cells (GCs) of PCOS patients and explore novel therapeutic targets for PCOS. METHODS: Randomized controlled trial was applied and a total of 72 women were included in the study, including 36 cases of PCOS patients and 36 cases of health controls...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28078823/hippo-vs-crab-tissue-specific-functions-of-the-mammalian-hippo-pathway
#13
REVIEW
Miki Nishio, Tomohiko Maehama, Hiroki Goto, Keisuke Nakatani, Wakako Kato, Hirofumi Omori, Yosuke Miyachi, Hideru Togashi, Yohei Shimono, Akira Suzuki
The Hippo signaling pathway is a vital suppressor of tumorigenesis that is often inactivated in human cancers. In normal cells, the Hippo pathway is triggered by external forces such as cell crowding, or changes to the extracellular matrix or cell polarity. Once activated, Hippo signaling down-regulates transcription supported by the paralogous cofactors YAP1 and TAZ. The Hippo pathway's functions in normal and cancer biology have been dissected by studies of mutant mice with null or conditional tissue-specific mutations of Hippo signaling elements...
January 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28076850/transforming-growth-factor-beta1-suppresses-hepatocellular-carcinoma-proliferation-via-activation-of-hippo-signaling
#14
Xiaodong Zhang, Qing Fan, Yan Li, Zhaoguo Yang, Liang Yang, Zhihong Zong, Biao Wang, Xin Meng, Qin Li, Jingang Liu, Hangyu Li
In this study, we examined the expression of core proteins of the Hippo signaling pathway in hepatocellular carcinoma (HCC) cells treated with transforming growth factor-β 1(TGF-β1) and investigated the relationship between TGF-β1 and the Hippo signaling pathway, in order to better understand their roles in HCC and their potential implications for cancer therapy. We prove that the Hippo signaling pathway is involved in the TGF-β1-induced inhibition of the growth of HCC cells. Large tumor suppressor expression (LATS1) was overexpression and yes association protein 1(YAP1) translocated from the nucleus to the cytoplasm in HCC cells treated with TGF-β1...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28067668/adaptor-proteins-numb-and-numbl-promote-cell-cycle-withdrawal-by-targeting-erbb2-for-degradation
#15
Maretoshi Hirai, Yoh Arita, C Jane McGlade, Kuo-Fen Lee, Ju Chen, Sylvia M Evans
Failure of trabecular myocytes to undergo appropriate cell cycle withdrawal leads to ventricular noncompaction and heart failure. Signaling of growth factor receptor ERBB2 is critical for myocyte proliferation and trabeculation. However, the mechanisms underlying appropriate downregulation of trabecular ERBB2 signaling are little understood. Here, we have found that the endocytic adaptor proteins NUMB and NUMBL were required for downregulation of ERBB2 signaling in maturing trabeculae. Loss of NUMB and NUMBL resulted in a partial block of late endosome formation, resulting in sustained ERBB2 signaling and STAT5 activation...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28060864/a-major-facilitator-superfamily-transporter-mediated-resistance-to-oxidative-stress-and-fungicides-requires-yap1-skn7-and-map-kinases-in-the-citrus-fungal-pathogen-alternaria-alternata
#16
Li-Hung Chen, Hsieh-Chin Tsai, Pei-Ling Yu, Kuang-Ren Chung
Major Facilitator Superfamily (MFS) transporters play an important role in multidrug resistance in fungi. We report an AaMFS19 gene encoding a MFS transporter required for cellular resistance to oxidative stress and fungicides in the phytopathogenic fungus Alternaria alternata. AaMFS19, containing 12 transmembrane domains, displays activity toward a broad range of substrates. Fungal mutants lacking AaMFS19 display profound hypersensitivities to cumyl hydroperoxide, potassium superoxide, many singlet oxygen-generating compounds (eosin Y, rose Bengal, hematoporphyrin, methylene blue, and cercosporin), and the cell wall biosynthesis inhibitor, Congo red...
2017: PloS One
https://www.readbyqxmd.com/read/28036290/yes-associated-protein-1-promotes-papillary-thyroid-cancer-cell-proliferation-by-activating-the-erk-mapk-signaling-pathway
#17
Tian Liao, Duo Wen, Ben Ma, Jia-Qian Hu, Ning Qu, Rong-Liang Shi, Liang Liu, Qing Guan, Duan-Shu Li, Qing-Hai Ji
Yes-associated protein 1 (YAP1) stimulates cell proliferation, epithelial-to-mesenchymal transition, invasion and metastasis in several cancers. Here, we investigated the involvement of YAP1 in papillary thyroid carcinoma (PTC) by assessing YAP1 mRNA and protein levels in PTC tissues and matched normal thyroid epithelial tissues from 50 patients. YAP1 mRNA and protein levels were higher in PTC tumor tissues than in control tissues, and correlated positively with the levels of proliferation-related genes (KI67 and c-MYC)...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28000790/a-cell-autonomous-tumour-suppressor-role-of-raf1-in-hepatocarcinogenesis
#18
Ines Jeric, Gabriele Maurer, Anna Lina Cavallo, Josipa Raguz, Enrico Desideri, Bartosz Tarkowski, Matthias Parrini, Irmgard Fischer, Kurt Zatloukal, Manuela Baccarini
Hepatocellular carcinoma (HCC) is a leading cause of cancer deaths, but its molecular heterogeneity hampers the design of targeted therapies. Currently, the only therapeutic option for advanced HCC is Sorafenib, an inhibitor whose targets include RAF. Unexpectedly, RAF1 expression is reduced in human HCC samples. Modelling RAF1 downregulation by RNAi increases the proliferation of human HCC lines in xenografts and in culture; furthermore, RAF1 ablation promotes chemical hepatocarcinogenesis and the proliferation of cultured (pre)malignant mouse hepatocytes...
December 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27993976/osteocrin-a-peptide-secreted-from-the-heart-and-other-tissues-contributes-to-cranial-osteogenesis-and-chondrogenesis-in-zebrafish
#19
Ayano Chiba, Haruko Watanabe-Takano, Kenta Terai, Hajime Fukui, Takahiro Miyazaki, Mami Uemura, Hisashi Hashimoto, Masahiko Hibi, Shigetomo Fukuhara, Naoki Mochizuki
The heart is an endocrine organ, as cardiomyocytes (CMs) secrete natriuretic peptide (NP) hormones. Since the discovery of NPs, no other peptide hormones that affect remote organs have been identified from the heart. We identified osteocrin (Ostn) as an osteogenesis/chondrogenesis regulatory hormone secreted from CMs in zebrafish. ostn mutant larvae exhibit impaired membranous and chondral bone formation. The impaired bones were recovered by CM-specific overexpression of OSTN. We analyzed the parasphenoid (ps) as a representative of membranous bones...
January 15, 2017: Development
https://www.readbyqxmd.com/read/27966820/overexpression-of-tead4-in-atypical-teratoid-rhabdoid-tumor-new-insight-to-the-pathophysiology-of-an-aggressive-brain-tumor
#20
Mario Suzuki, Akihide Kondo, Ikuko Ogino, Hajime Arai, Tadanori Tomita, Simone Treiger Sredni
BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant embryonal brain tumor that occurs mainly in early childhood. Although most of the tumors are characterized by inactivating mutations of the tumor suppressor gene, SMARCB1, the biological basis of its tumorigenesis and aggressiveness is still unknown. PROCEDURE: We performed high-throughput copy number variation analysis of primary cell lines generated from primary and relapsed tumors from one of our patients to identify new genes involved in AT/RT biology...
December 14, 2016: Pediatric Blood & Cancer
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