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https://www.readbyqxmd.com/read/29346075/human-papillomavirus-e6-interaction-with-cellular-pdz-domain-proteins-modulates-yap-nuclear-localization
#1
Sydney Webb Strickland, Nicole Brimer, Charles Lyons, Scott B Vande Pol
HPV E6 oncoproteins associate with cellular PDZ proteins. In addition to previously identified cellular PDZ proteins, we found association of the HPV16 E6 PBM with the Dystrophin Glycoprotein Complex, LRCC1, and SLC9A3R2. HPV18 E6 had additional associations when lysates from adenomatous cell lines were used including LRPPRC, RLGAPB, EIF3A, SMC2 and 3, AMOT, AMOTL1, and ARHGEF1; some of these cellular PDZ proteins are implicated in the regulation of the YAP1 transcriptional co-activator. In keratinocytes, nuclear translocation of YAP1 was promoted by the complete HPV-16 genome, or by expression of the individual E6 or E7 oncoproteins; the activity of E6 required an intact PBM at the carboxy-terminus...
January 12, 2018: Virology
https://www.readbyqxmd.com/read/29342503/the-molecular-basis-for-dysregulated-activation-of-nkx2-5-in-vascular-remodelling-of-systemic-sclerosis
#2
Athina Dritsoula, Ioannis Papaioannou, Sandra G Guerra, Carmen Fonseca, Javier Martin, Ariane L Herrick, David J Abraham, Christopher P Denton, Markella Ponticos
OBJECTIVE: NKX2-5 is a homeobox transcription factor required for the formation of the heart and vessels during development, with significant postnatal downregulation and reactivation in disease states characterised by vascular remodelling. In this study, we sought to investigate mechanisms that activate NKX2-5 expression in diseased vessels, such as scleroderma associated pulmonary hypertension (SSc-PH), and identify genetic variability that potentially underlies susceptibility to specific vascular complications...
January 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29340043/clinical-significance-of-yap1-activation-in-head-and-neck-squamous-cell-carcinoma
#3
Young-Gyu Eun, Dongjin Lee, Young Chan Lee, Bo Hwa Sohn, Eui Hyun Kim, Sun Young Yim, Kee Hwan Kwon, Ju-Seog Lee
By analyzing the genomic data of head and neck squamous cell cancer (HNSCC), we investigated clinical significance of YAP1 activation. Copy number and mRNA expression of YAP1 were analyzed together to assess clinical relevance of YAP1 activation in HNSCC. The clinical significance of YAP1 activation was further validated in four independent test cohorts. We also assessed the correlation of YAP1 activation with genomic alterations such as copy number alteration, somatic mutation, and miRNA expression. The YAP1-activated (YA) subgroup showed worse prognosis for HNSCC as tested and validated in five cohorts...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29329575/microrna-200a-confers-chemoresistance-by-antagonizing-tp53inp1-and-yap1-in-human-breast-cancer
#4
San-Jian Yu, Liu Yang, Qi Hong, Xia-Ying Kuang, Gen-Hong Di, Zhi-Ming Shao
BACKGROUND: Emerging evidence suggests molecular and phenotypic association between treatment resistance and epithelial-mesenchymal transition (EMT) in cancer. Compared with the well-defined molecular events of miR-200a in EMT, the role of miR-200a in therapy resistance remains to be elucidated. METHODS: Breast cancer cells transfected with mimic or inhibitor for miR-200a was assayed for chemoresistance in vitro. miR-200a expression was assessed by quantitative real-time PCR (qRT-PCR) in breast cancer patients treated with preoperative chemotherapy...
January 12, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29316729/wnt-rspo-and-hippo-signalling-in-the-intestine-and-intestinal-stem-cells
#5
REVIEW
Vitezslav Kriz, Vladimir Korinek
In this review, we address aspects of Wnt, R-Spondin (RSPO) and Hippo signalling, in both healthy and transformed intestinal epithelium. In intestinal stem cells (ISCs), the Wnt pathway is essential for intestinal crypt formation and renewal, whereas RSPO-mediated signalling mainly affects ISC numbers. In human colorectal cancer (CRC), aberrant Wnt signalling is the driving mechanism initiating this type of neoplasia. The signalling role of the RSPO-binding transmembrane proteins, the leucine-rich-repeat-containing G-protein-coupled receptors (LGRs), is possibly more pleiotropic and not only limited to the enhancement of Wnt signalling...
January 8, 2018: Genes
https://www.readbyqxmd.com/read/29312609/ascl2-activation-by-yap1-klf5-ensures-the-self-renewability-of-colon-cancer-progenitor-cells
#6
Xiaolong Wei, Jun Ye, Yangyang Shang, Haoyuan Chen, Shanxi Liu, Li Liu, Rongquan Wang
Achaete scute-like 2 (Ascl2) is the Wnt signaling target, its regulation by other signaling is undefined. Now we demonstrated that CD133+/CD44+ cell population from HT-29 or Caco-2 cells exhibited cancer stem cell (CSC) properties with highly expressed Ascl2, which is related to the Hippo signaling pathway. YAP1 interference in CD133+/CD44+ HT-29 or Caco-2 cells reduced their proliferation, colony-forming ability and tumorsphere formation in vitro and inhibited the 'stemness'-associated genes and Ascl2 expression...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29305935/hedgehog-yap-signaling-pathway-regulates-glutaminolysis-to-control-hepatic-stellate-cell-activation
#7
Kuo Du, Jeongeun Hyun, Richard T Premont, Steve S Choi, Gregory A Michelotti, Marzena Swiderska-Syn, George D Dalton, Eric Thelen, Bahar Salimian Rizi, Youngmi Jung, Anna Mae Diehl
BACKGROUND & AIMS: Cirrhosis results from accumulation of myofibroblasts derived from quiescent hepatic stellate cells (Q-HSCs); it regresses when myofibroblastic HSCs are depleted. Hedgehog signaling promotes transdifferentiation of HSCs by activating Yes-associated protein 1 (YAP1 or YAP) and inducing aerobic glycolysis. However, increased aerobic glycolysis alone cannot meet the high metabolic demands of myofibroblastic HSCs. Determining the metabolic processes of these cells could lead to strategies to prevent progressive liver fibrosis, so we investigated whether glutaminolysis (conversion of glutamine to alpha-ketoglutarate) sustains energy metabolism and permits anabolism when Q-HSCs become myofibroblastic, and whether this is controlled by hedgehog signaling to YAP...
January 3, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29299145/inhibition-of-yap-function-overcomes-braf-inhibitor-resistance-in-melanoma-cancer-stem-cells
#8
Matthew L Fisher, Daniel Grun, Gautam Adhikary, Wen Xu, Richard L Eckert
Treating BRAF inhibitor-resistant melanoma is an important therapeutic goal. Thus, it is important to identify and target mechanisms of resistance to improve therapy. The YAP1 and TAZ proteins of the Hippo signaling pathway are important drivers of cancer cell survival, and are BRAF inhibitor resistant factors in melanoma. We examine the role of YAP1/TAZ in melanoma cancer stem cells (MCS cells). We demonstrate that YAP1, TAZ and TEAD (TEA domain transcription factor) levels are elevated in BRAF inhibitor resistant MCS cells and enhance cell survival, spheroid formation, matrigel invasion and tumor formation...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296212/small-sized-colorectal-cancer-cells-harbor-metastatic-tumor-initiating-cells
#9
Lei Mu, Kaiyu Huang, Yibing Hu, Chang Yan, Xiaolan Li, Deding Tao, Jianping Gong, Jichao Qin
Colorectal cancer (CRC) is heterogeneous and contains different-sized cells. Recent studies have shown that tumor-initiating cells (TICs) are involved in cancer initiation, recurrence and metastasis. However, connections between cancer cell size and stem-like properties are largely unknown. Here we purified large- and small-sized CRC cells by fluorescence-activated cell sorting (FACS) based on forward scatter (FSC), and demonstrated that small CRC cells possess higher holoclone- and sphere-forming capacity in vitro, tumor-initiating capacity in vivo and form more lung metastases compared with large CRC cells...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296196/antitumor-effects-of-the-antiparasitic-agent-ivermectin-via-inhibition-of-yes-associated-protein-1-expression-in-gastric-cancer
#10
Sho Nambara, Takaaki Masuda, Miki Nishio, Shotaro Kuramitsu, Taro Tobo, Yushi Ogawa, Qingjiang Hu, Tomohiro Iguchi, Yousuke Kuroda, Shuhei Ito, Hidetoshi Eguchi, Keishi Sugimachi, Hiroshi Saeki, Eiji Oki, Yoshihiko Maehara, Akira Suzuki, Koshi Mimori
Yes-associated protein 1 (YAP1) acts as an oncogene through dephosphorylation and nuclear translocation, and nuclear accumulation of YAP1 is associated with poor prognosis in gastric cancer (GC). We previously identified ivermectin, an antiparasitic drug, as a YAP1 inhibitor. Here, we aimed to clarify whether ivermectin had antitumor effects on GC through inhibition of YAP1. First, we evaluated the antiproliferative effects of ivermectin on human GC cells using in vitro proliferation assays and a xenograft mouse model...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29286919/knockdown-of-lncrna-ghet1-suppresses-cell-proliferation-invasion-and-lats1-yap-pathway-in-non-small-cell-lung-cancer
#11
Zhen-Biao Guan, Yu-Shu Cao, Yi Li, Wan-Ning Tong, An-Shan Zhuo
BACKGROUND: The aim in this study was to explore the role of long non-coding RNA GHET1 in development of non small cell lung cancer (NSCLC). METHODS: LncRNA GHET1 expression levels were analyzed by qRT-PCR in tumor tissues and adjacent normal tissues in NSCLC. Measuring the cell proliferation and invasion abilities by CCK8, cell colony formation and transwell invasion assays. Relative protein expression was analyzed by western blot assays. RESULTS: Expression of lncRNA GHET1 was notably higher in NSCLC tissues compared with adjacent normal tissues by using qRT-PCR analyses...
December 22, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29285076/niu-huang-shen-suppresses-hepatocellular-carcinoma-cell-growth-and-metastasis-by-regulating-yap1-expression
#12
Yanfang Peng, Yingqian Zhao, Taisheng Ye, Yabing Zhang, Zhaoyan Wu, Yukun Xia, Yingwen Zhang
Hepatocellular carcinoma (HCC) is one of the most common cancers types. Niu-Huang-Shen (NHS), a Chinese medicine, has been reported to exert antipyretic, anti-inflammatory and vasodilatation effects. However, whether NHS has inhibitory effects on HCC cell phenotypes has remained elusive. In the present study, Cell Counting Kit-8, colony formation, fluorescence-activated cell sorting and Transwell assays were used to evaluate the effect of NHS on cell proliferation, migration and invasion. The results indicated that NHS suppressed cell proliferation and invasion, inhibited cell apoptosis, and induced cell cycle arrest...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29283341/regulation-of-posterior-body-and-epidermal-morphogenesis-in-zebrafish-by-localized-yap1-and-wwtr1
#13
David Kimelman, Natalie L Smith, Jason Kuan Han Lai, Didier Yr Stainier
The vertebrate embryo undergoes a series of dramatic morphological changes as the body extends to form the complete anterior-posterior axis during the somite-forming stages. The molecular mechanisms regulating these complex processes are still largely unknown. We show that the Hippo pathway transcriptional coactivators Yap1 and Wwtr1 are specifically localized to the presumptive epidermis and notochord, and play a critical and unexpected role in posterior body extension by regulating Fibronectin assembly underneath the presumptive epidermis and surrounding the notochord...
December 28, 2017: ELife
https://www.readbyqxmd.com/read/29258295/therapeutic-targeting-of-ependymoma-as-informed-by-oncogenic-enhancer-profiling
#14
Stephen C Mack, Kristian W Pajtler, Lukas Chavez, Konstantin Okonechnikov, Kelsey C Bertrand, Xiuxing Wang, Serap Erkek, Alexander Federation, Anne Song, Christine Lee, Xin Wang, Laura McDonald, James J Morrow, Alina Saiakhova, Patrick Sin-Chan, Qiulian Wu, Kulandaimanuvel Antony Michaelraj, Tyler E Miller, Christopher G Hubert, Marina Ryzhova, Livia Garzia, Laura Donovan, Stephen Dombrowski, Daniel C Factor, Betty Luu, Claudia L L Valentim, Ryan C Gimple, Andrew Morton, Leo Kim, Briana C Prager, John J Y Lee, Xiaochong Wu, Jennifer Zuccaro, Yuan Thompson, Borja L Holgado, Jüri Reimand, Susan Q Ke, Adam Tropper, Sisi Lai, Senthuran Vijayarajah, Sylvia Doan, Vaidehi Mahadev, Ana Fernandez Miñan, Susanne N Gröbner, Matthias Lienhard, Marc Zapatka, Zhiqin Huang, Kenneth D Aldape, Angel M Carcaboso, Peter J Houghton, Stephen T Keir, Till Milde, Hendrik Witt, Yan Li, Chao-Jun Li, Xiu-Wu Bian, David T W Jones, Ian Scott, Sheila K Singh, Annie Huang, Peter B Dirks, Eric Bouffet, James E Bradner, Vijay Ramaswamy, Nada Jabado, James T Rutka, Paul A Northcott, Mathieu Lupien, Peter Lichter, Andrey Korshunov, Peter C Scacheri, Stefan M Pfister, Marcel Kool, Michael D Taylor, Jeremy N Rich
Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy...
December 20, 2017: Nature
https://www.readbyqxmd.com/read/29228705/yap1-inhibition-radiosensitizes-triple-negative-breast-cancer-cells-by-targeting-the-dna-damage-response-and-cell-survival-pathways
#15
Daniel Andrade, Meghna Mehta, James Griffith, Janani Panneerselvam, Akhil Srivastava, Tae-Dong Kim, Ralf Janknecht, Terence Herman, Rajagopal Ramesh, Anupama Munshi
The Hippo pathway is an evolutionarily conserved signaling pathway that regulates proliferation and apoptosis to control organ size during developmental growth. Yes-associated protein 1 (YAP1), the terminal effector of the Hippo pathway, is a transcriptional co-activator and a potent growth promoter that has emerged as a critical oncogene. Overexpression of YAP1 has been implicated in promoting resistance to chemo-, radiation and targeted therapy in various cancers. However, the role of YAP1 in radioresistance in triple-negative breast cancer (TNBC) is currently unknown...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228123/role-of-yes-associated-protein-1-angiomotin-and-mitogen-activated-kinase-kinase-1-2-in-development-of-the-bovine-blastocyst
#16
Verónica M Negrón-Pérez, Peter J Hansen
The morula-stage embryo is transformed into a blastocyst composed of epiblast, hypoblast and trophectoderm (TE) through mechanisms that, at least in the mouse, involve the Hippo signaling and mitogen-activated kinase (MAPK) pathways. Using the cow as an additional model, we tested the hypotheses that TE and hypoblast differentiation were regulated by the Hippo pathway regulators, YAP1 and AMOT, and MAPK kinase 1/2 (MAPK1/2). The presence of YAP1 and CDX2 in the nucleus and cytoplasm of MII oocytes and embryos was evaluated by immunofluorescence labeling...
December 8, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29215734/study-on-mechanism-about-long-noncoding-rna-malat1-affecting-pancreatic-cancer-by-regulating-hippo-yap-signaling
#17
Yongping Zhou, Ting Shan, Wenzhou Ding, Zhiyuan Hua, Yijun Shen, Zhihua Lu, Bo Chen, Tu Dai
OBJECTIVE: By investigating the migration and invasion ability in pancreatic cancer, this study probed into the lncRNA MALAT1 molecular mechanism on Hippo-YAP signaling. METHODS: The expression of lncRNA MALAT1 in PC tissues and cells was detected by qRT-PCR and western blot. The effect of si-MALAT1 on proliferation was determined by CCK-8 assay. Cell apoptosis, migration and invasion were respectively detected by flow cytometry assay, wound healing assay and transwell assay...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29212185/hyaluronic-acid-enhances-cell-migration-and-invasion-via-the-yap1-taz-rhamm-axis-in-malignant-pleural-mesothelioma
#18
Wataru Shigeeda, Masahiko Shibazaki, Shinji Yasuhira, Tomoyuki Masuda, Tatsuo Tanita, Yuka Kaneko, Tatsuhiro Sato, Yoshitaka Sekido, Chihaya Maesawa
Most malignant mesotheliomas (MPMs) frequently show activated forms of Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which transcriptionally regulates the receptor for hyaluronic acid-mediated motility (RHAMM). As RHAMM is involved in cell migration and invasion in various tumors, we speculated that hyaluronic acid (HA) in pleural fluid might affect the progression of mesothelioma by stimulating cell migration and invasion through RHAMM. The level of RHAMM expression was decreased by YAP1/TAZ knockdown, and conversely increased by forced expression of the active form of YAP1, suggesting that RHAMM was regulated by YAP1/TAZ in MPM cells...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29187885/huaier-restrains-proliferative-and-migratory-potential-of-hepatocellular-carcinoma-cells-partially-through-decreased-yes-associated-protein-1
#19
Liang Shan, Yan Li, Hongyuan Jiang, Yuquan Tao, Zijun Qian, Lan Li, Feng Cai, Lifang Ma, Yongchun Yu
In China, Trametes robiniophila Murr (Huaier), a traditional Chinese herbal medicine, has been widely used in adjuvant therapies of hepatocellular carcinoma (HCC). However, the molecular mechanisms have not been fully understood. The aims of this study are to investigate the functions and mechanisms of Huaier on inhibiting proliferation and migration of HCC cells. Firstly, cell counting kit-8 (CCK-8) and colony formation shown Huaier inhibited proliferation of HCC Bel-7404, Bel-7402 and SMMC-7721 cells in a dose-dependent manner, and this inhibition might be due to Huaier decreased the expressions of the proliferating cell nuclear antigen (PCNA), the nuclear proliferation related antigen (Ki-67) and CyclinD1 detected by western blotting analysis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29180467/yap1-and-cox2-coordinately-regulate-urothelial-cancer-stem-like-cells
#20
Akira Ooki, Maria Del Carmen Rodriguez Pena, Luigi Marchionni, Wikum Dinalankara, Asma Begum, Noah M Hahn, Christopher J VandenBussche, Zeshaan A Rasheed, Shifeng Mao, George J Netto, David Sidransky, Mohammad O Hoque
Overcoming acquired drug resistance remains a core challenge in the clinical management of human cancer, including in urothelial carcinoma of the bladder (UCB). Cancer stem-like cells (CSC) have been implicated in the emergence of drug resistance but mechanisms and intervention points are not completely understood. Here we report that the pro-inflammatory COX2/PGE2 pathway and the YAP1 growth regulatory pathway cooperate to recruit the stem cell factor SOX2 in expanding and sustaining the accumulation of urothelial CSC...
November 27, 2017: Cancer Research
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