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https://www.readbyqxmd.com/read/28102225/glucocorticoid-receptor-signalling-activates-yap-in-breast-cancer
#1
Giovanni Sorrentino, Naomi Ruggeri, Alessandro Zannini, Eleonora Ingallina, Rebecca Bertolio, Carolina Marotta, Carmelo Neri, Elisa Cappuzzello, Mattia Forcato, Antonio Rosato, Miguel Mano, Silvio Bicciato, Giannino Del Sal
The Hippo pathway is an oncosuppressor signalling cascade that plays a major role in the control of cell growth, tissue homoeostasis and organ size. Dysregulation of the Hippo pathway leads to aberrant activation of the transcription co-activator YAP (Yes-associated protein) that contributes to tumorigenesis in several tissues. Here we identify glucocorticoids (GCs) as hormonal activators of YAP. Stimulation of glucocorticoid receptor (GR) leads to increase of YAP protein levels, nuclear accumulation and transcriptional activity in vitro and in vivo...
January 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28099921/stiehopus-japonieus-acidic-mucopolysaccharide-inhibits-the-proliferation-of-pancreatic-cancer-sw1990-cells-through-hippo-yap-pathway
#2
Xiaoyu Li, Yi Liu, Cuiping Zhang, Qinghui Niu, Hui Wang, Cong Che, Man Xie, Bin Zhou, Yonghong Xu, Qi Zhang, Jun Wu, Zibin Tian
Previous studies have indicated that stiehopus japonieus acidic mucopolysaccharide (SJAMP) could inhibit the proliferation of pancreatic cancer cell SW1990. However, the mechanism remains unclear. In our study, YAP expression was identified by immunohistochemistry and quantitative Real-time PCR from 45 pairs of human pancreatic ductal adenocarcinoma (PDAC) tissues and their adjacent non-tumor samples. We found that the YAP expression was associated with the histological differentiation degree, and negatively correlated with pancreatic cancer patients' survival...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088685/a-semi-interpenetrating-network-of-polyacrylamide-and-recombinant-basement-membrane-allows-pluripotent-cell-culture-in-a-soft-ligand-rich-microenvironment
#3
Andrew J Price, Eva Y Huang, Vittorio Sebastiano, Alexander R Dunn
The physical properties of the extracellular matrix play an essential role in guiding stem cell differentiation and tissue morphogenesis both in vivo and in vitro. Existing work to investigate the role of matrix mechanics in directing stem cell proliferation, self-renewal, and differentiation has been limited by the poor attachment and survival of human pluripotent cells cultured on soft matrices (Young's modulus E ≲ 1000 Pa). To address this limitation we developed a protocol for generating semi-interpenetrating networks of polyacrylamide and recombinant basement membrane...
December 9, 2016: Biomaterials
https://www.readbyqxmd.com/read/28076326/cytosolic-thumpd1-promotes-breast-cancer-cells-invasion-and-metastasis-via-the-akt-gsk3-snail-pathway
#4
Xiupeng Zhang, Guiyang Jiang, Mingfang Sun, Haijing Zhou, Yuan Miao, Mengyuan Liang, Enhua Wang, Yong Zhang
Human THUMP domain-containing protein 1 (THUMPD1) is a specific adaptor protein that modulates tRNA acetylation through interaction with NAT10. Immunohistochemical analysis of 146 breast cancer specimens (82 triple-negative and 64 non-triple-negative cases) indicated THUMPD1 expression is higher in breast cancer tissues (60.9%, 89/146) than normal breast tissues (28.3%, 15/53; p < 0.001). Overall and cytosolic, but not nuclear, THUMPD1 expression in breast cancer correlated with advanced TNM stage (p = 0...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28068668/the-hippo-kinases-lats1-and-2-control-human-breast-cell-fate-via-crosstalk-with-er%C3%AE
#5
Adrian Britschgi, Stephan Duss, Sungeun Kim, Joana Pinto Couto, Heike Brinkhaus, Shany Koren, Duvini De Silva, Kirsten D Mertz, Daniela Kaup, Zsuzsanna Varga, Hans Voshol, Alexandra Vissieres, Cedric Leroy, Tim Roloff, Michael B Stadler, Christina H Scheel, Loren J Miraglia, Anthony P Orth, Ghislain M C Bonamy, Venkateshwar A Reddy, Mohamed Bentires-Alj
Cell fate perturbations underlie many human diseases, including breast cancer. Unfortunately, the mechanisms by which breast cell fate are regulated are largely unknown. The mammary gland epithelium consists of differentiated luminal epithelial and basal myoepithelial cells, as well as undifferentiated stem cells and more restricted progenitors. Breast cancer originates from this epithelium, but the molecular mechanisms that underlie breast epithelial hierarchy remain ill-defined. Here, we use a high-content confocal image-based short hairpin RNA screen to identify tumour suppressors that regulate breast cell fate in primary human breast epithelial cells...
January 9, 2017: Nature
https://www.readbyqxmd.com/read/28061504/dub3-deubiquitylating-enzymes-regulate-hippo-pathway-activity-by-regulating-the-stability-of-itch-lats-and-amot-proteins
#6
Hung Thanh Nguyen, Jan-Michael Kugler, Stephen M Cohen
The YAP and TAZ transcriptional coactivators promote oncogenic transformation. Elevated YAP/TAZ activity has been documented in human tumors. YAP and TAZ are negatively regulated by the Hippo tumor suppressor pathway. The activity and stability of several Hippo pathway components, including YAP/TAZ, is regulated by ubiquitin mediated protein turnover and several ubiquitin ligase complexes have been implicated in human cancer. However, little is known about the deubiquitylating enzymes that counteract these ubiquitin ligases in regulation of the Hippo pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28052036/angiomotin-regulates-prostate-cancer-cell-proliferation-by-signaling-through-the-hippo-yap-pathway
#7
Hao Zeng, Angelica Ortiz, Peng-Fei Shen, Chien-Jui Cheng, Yu-Chen Lee, Guoyu Yu, Song-Chang Lin, Chad J Creighton, Li-Yuan Yu-Lee, Sue-Hwa Lin
Angiomotin (AMOT) is a family of proteins found to be a component of the apical junctional complex of vertebrate epithelial cells and is recently found to play important roles in neurofibromatosis type 2 (NF-2). Whether AMOT plays a role in prostate cancer (PCa) is unknown. AMOT is expressed as two isoforms, AMOTp80 and AMOTp130, which has a 409 aa N-terminal domain that is absent in AMOTp80. Both AMOTp80 and AMOTp130 are expressed in LNCaP and C4-2B4, but at a low to undetectable level in PC3, DU145, and BPH1 cells...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28051067/vgll4-targets-a-tcf4-tead4-complex-to-coregulate-wnt-and-hippo-signalling-in-colorectal-cancer
#8
Shi Jiao, Chuanchuan Li, Qian Hao, Haofei Miao, Lei Zhang, Lin Li, Zhaocai Zhou
Concerted co-regulation of multiple signalling pathways is crucial for tissue homoeostasis and tumorigenesis. Here we report that VGLL4, a previously identified YAP antagonist, also functions as a regulator of Wnt/β-catenin signalling. The expression of VGLL4 is significantly downregulated in clinical colorectal carcinoma (CRC) specimens, positively associated with patient survival rate, and inversely correlated with the expression of Wnt target genes in CRCs. Knockdown of VGLL4 enhances proliferation and tumour formation of CRC cells...
January 4, 2017: Nature Communications
https://www.readbyqxmd.com/read/28042766/insights-into-the-regulation-of-yap-taz-from-cellular-systems-and-mouse-models
#9
Wei Du, Wen Du, Mian Wan, Xuedong Zhou, Xin Xu, Liwei Zheng
The Hippo signaling pathway serves as a main regulator of tissue growth and organ size through the moderation of cell cycle dynamics across many different species. In mammals, the two downstream transcriptional regulators of this pathway are Yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ). Recent studies found in addition to the core Hippo signaling pathway, other signaling pathways can also regulate YAP/TAZ activity, either directly or through crosstalk with the Hippo pathway...
January 2, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28041841/actl6a-is-co-amplified-with-p63-in-squamous-cell-carcinoma-to-drive-yap-activation-regenerative-proliferation-and-poor-prognosis
#10
Srinivas Vinod Saladi, Kenneth Ross, Mihriban Karaayvaz, Purushothama R Tata, Hongmei Mou, Jayaraj Rajagopal, Sridhar Ramaswamy, Leif W Ellisen
Loss-of-function mutations in SWI/SNF chromatin-remodeling subunit genes are observed in many cancers, but an oncogenic role for SWI/SNF is not well established. Here, we reveal that ACTL6A, encoding an SWI/SNF subunit linked to stem cell and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC). ACTL6A and p63 physically interact, cooperatively controlling a transcriptional program that promotes proliferation and suppresses differentiation, in part through activation of the Hippo-YAP pathway via regulators including WWC1...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28035075/the-hippo-signaling-pathway-provides-novel-anti-cancer-drug-targets
#11
REVIEW
June Sung Bae, Sun Mi Kim, Ho Lee
The Hippo signaling pathway plays a crucial role in cell proliferation, apoptosis, differentiation, and development. Major effectors of the Hippo signaling pathway include the transcriptional co-activators Yes-associated protein 1 (YAP) and WW domain-containing transcription regulator protein 1 (TAZ). The transcriptional activities of YAP and TAZ are affected by interactions with proteins from many diverse signaling pathways as well as responses to the external environment. High YAP and TAZ activity has been observed in many cancer types, and functional dysregulation of Hippo signaling enhances the oncogenic properties of YAP and TAZ and promotes cancer development...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28018981/splice-variant-insertions-in-the-c-terminus-impairs-yap-s-transactivation-domain
#12
Megan L Finch-Edmondson, Robyn P Strauss, Joshua S Clayton, George C Yeoh, Bernard A Callus
The yes-associated protein (YAP) is a key effector of the mammalian Hippo signaling pathway. YAP has eight known alternately spliced isoforms and these are widely expressed across multiple tissues. Variable effects have been ascribed to different YAP isoforms by inducing their expression in cells, but whether these differences are due to variability in the transcriptional potency of individual YAP isoforms has not been addressed. Indeed a systematic comparison of the transcriptional potencies of YAP isoforms has not been done...
July 2016: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28004182/cdk5rap2-interaction-with-components-of-the-hippo-signaling-pathway-may-play-a-role-in-primary-microcephaly
#13
Salil K Sukumaran, Maria Stumpf, Sarah Salamon, Ilyas Ahmad, Kurchi Bhattacharya, Sarah Fischer, Rolf Müller, Janine Altmüller, Birgit Budde, Holger Thiele, Muhammad Tariq, Naveed Altaf Malik, Peter Nürnberg, Shahid Mahmood Baig, Muhammad Sajid Hussain, Angelika A Noegel
Autosomal recessive primary microcephaly (MCPH) is characterized by a substantial reduction in brain size but with normal architecture. It is often linked to mutations in genes coding for centrosomal proteins; however, their role in brain size regulation is not completely understood. By combining homozygosity mapping and whole-exome sequencing in an MCPH family from Pakistan, we identified a novel mutation (XM_011518861.1; c.4114C > T) in CDK5RAP2, the gene associated with primary microcephaly-3 (MCPH3), leading to a premature stop codon (p...
December 21, 2016: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28003305/co-occurring-mutations-of-tumor-suppressor-genes-lats2-and-nf2-in-malignant-pleural-mesothelioma
#14
Robin Tranchant, Lisa Quetel, Anne Tallet, Clément Meiller, Annie Renier, Leanne de Koning, Aurélien de Reyniès, Francoise Le Pimpec Barthes, Jessica Zucman-Rossi, Marie-Claude Jaurand, Didier Jean
PURPOSE: To better define MPM heterogeneity and identify molecular subtypes of malignant pleural mesothelioma (MPM), we focus on the tumor suppressor gene LATS2, a member of the Hippo signaling pathway, which plays a key role in mesothelial carcinogenesis. EXPERIMENTAL DESIGN: Sixty-one MPM primary cultures established in our laboratory were screened for mutations in LATS2. Gene inactivation was modeled using siRNAs. Gene and protein expressions were analyzed by quantitative RT-PCR, western blot and RPPA...
December 21, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28003126/emerging-role-of-hippo-signalling-in-pancreatic-biology-yap-re-expression-and-plausible-link-to-islet-cell-apoptosis-and-replication
#15
REVIEW
Anjana Sharma, Veera Ganesh Yerra, Ashutosh Kumar
Diabetes mellitus is an ailment that develops when the functional capacity of the pancreas does not meet the metabolic requirements of the whole body, either due to insulin insufficiency or resistance to insulin action. Current therapies that control glycaemia are limited by their unwanted effects or their inability to prevent the development of long-term complications. Regeneration and replacement of beta cell therapies are shaping the goals of future management of diabetes. The Hippo pathway, first discovered in Drosophila melanogaster, plays a vital role in controlling the organ size...
December 18, 2016: Biochimie
https://www.readbyqxmd.com/read/28003097/hippo-signaling-in-the-liver-regulates-organ-size-cell-fate-and%C3%A2-carcinogenesis
#16
REVIEW
Sachin Patel, Fernando D Camargo, Dean Yimlamai
The Hippo signaling pathway, also known as the Salvador-Warts-Hippo pathway, is a regulator of organ size. The pathway takes its name from the Drosophila protein kinase, Hippo (STK4/MST1 and STK3/MST2 in mammals), which, when inactivated, leads to considerable tissue overgrowth. In mammals, MST1 and MST2 negatively regulate the transcriptional co-activators yes-associated protein 1 and WW domain containing transcription regulator 1 (WWTR1/TAZ), which together regulate expression of genes that control proliferation, survival, and differentiation...
December 19, 2016: Gastroenterology
https://www.readbyqxmd.com/read/28002618/verteporfin-suppresses-cell-survival-angiogenesis-and-vasculogenic-mimicry-of-pdac-via-disrupting-the-yap-tead-complex
#17
Honglong Wei, Fuhai Wang, Yong Wang, Tao Li, Peng Xiu, Jingtao Zhong, Xueying Sun, Jie Li
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies. The Yes-associated protein-1 (YAP) plays a critical role in cell proliferation, apoptosis and angiogenesis. Verteporfin is a photosensitizer used in photodynamic therapy and also a small molecular inhibitor of the Hippo-YAP pathway. However, little is known whether verteporfin could inhibit YAP activity in PDAC cells. Our present results showed that verteporfin suppressed the proliferation of human PDAC PANC-1 and SW1990 cells by arresting cells at G1 phase, and inducing apoptosis in dose- and time-dependent manners...
December 21, 2016: Cancer Science
https://www.readbyqxmd.com/read/27990121/targeting-mechanotransduction-at-the-transcriptional-level-yap-and-brd4-are-novel-therapeutic-targets-for-the-reversal-of-liver-fibrosis
#18
REVIEW
Altynbek Zhubanchaliyev, Aibar Temirbekuly, Kuralay Kongrtay, Leah C Wanshura, Jeannette Kunz
Liver fibrosis is the result of a deregulated wound healing process characterized by the excessive deposition of extracellular matrix. Hepatic stellate cells (HSCs), which are activated in response to liver injury, are the major source of extracellular matrix and drive the wound healing process. However, chronic liver damage leads to perpetual HSC activation, progressive formation of pathological scar tissue and ultimately, cirrhosis and organ failure. HSC activation is triggered largely in response to mechanosignaling from the microenvironment, which induces a profibrotic nuclear transcription program that promotes HSC proliferation and extracellular matrix secretion thereby setting up a positive feedback loop leading to matrix stiffening and self-sustained, pathological, HSC activation...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27987320/association-between-axl-hippo-transducers-and-survival-outcomes-in-male-breast-cancer
#19
Anna Di Benedetto, Marcella Mottolese, Francesca Sperati, Cristiana Ercolani, Luigi Di Lauro, Laura Pizzuti, Patrizia Vici, Irene Terrenato, Abeer M Shaaban, Matthew P Humphries, Sreekumar Sundara-Rajan, Maddalena Barba, Valerie Speirs, Ruggero De Maria, Marcello Maugeri-Saccà
Male breast cancer (MBC) is an uncommon malignancy. We have previously reported that the expression of the Hippo transducers TAZ/YAP and their target CTGF was associated with inferior survival in MBC patients. Preclinical evidence demonstrated that Axl is a transcriptional target of TAZ/YAP. Thus, we herein assessed AXL expression to further investigate the significance of active TAZ/YAP-driven transcription in MBC. For this study, 255 MBC samples represented in tissue microarrays were screened for AXL expression, and 116 patients were included...
December 17, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27979976/yap-needs-nemo-to-guide-a-hippo
#20
Alexander Hergovich
No abstract text is available yet for this article.
January 2017: EMBO Reports
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