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https://www.readbyqxmd.com/read/28213440/muscle-yap-is-a-regulator-of-neuromuscular-junction-formation-and-regeneration
#1
Kai Zhao, Chengyong Shen, Yisheng Lu, Zhihui Huang, Lei Li, Christopher D Rand, Jinxiu Pan, Xiang-Dong Sun, Zhibing Tan, Hongsheng Wang, Guanglin Xing, Yu Cao, Guoqing Hu, Jiliang Zhou, Wen-Cheng Xiong, Lin Mei
Yes-associated protein (Yap) is a major effector of the Hippo pathway that regulates cell proliferation and differentiation during development and restricts tissue growth in adult animals. However, its role in synapse formation remains poorly understood. In this study, we characterized Yap's role in the formation of neuromuscular junction (NMJ). In HSA-Yap(-/-) mice where Yap was mutated specifically in muscle cells, AChR clusters were smaller and were distributed in a broader region in the middle of muscle fibers, suggesting that muscle Yap is necessary for the size and location of AChR clusters...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28202507/yap-taz-mediated-upregulation-of-gab2-leads-to-increased-sensitivity-to-growth-factor-induced-activation-of-the-pi3k-pathway
#2
Chao Wang, Chao Gu, Kang Jin Jeong, Dong Zhang, Wei Guo, Yiling Lu, Zhenlin Ju, Nattapon Panupinthu, Ji Yeon Yang, Mihai Gagea, Patrick Kwok Shing Ng, Fan Zhang, Gordon B Mills
The transcription regulators YAP and TAZ function as effectors of the HIPPO signaling cascade, critical for organismal development, cell growth, and cellular reprogramming, and YAP/TAZ is commonly misregulated in human cancers. The precise mechanism by which aberrant YAP/TAZ promotes tumor growth remains unclear. The HIPPO tumor suppressor pathway phosphorylates YAP and TAZ resulting in cytosolic sequestration with subsequent degradation. Here we report that the phosphatidylinositol 3' kinase (PI3K)/AKT pathway, which is critically involved in the pathophysiology of endometrial cancer (EC), interacts with the HIPPO pathway at multiple levels...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28183853/mark4-inhibits-hippo-signaling-to-promote-proliferation-and-migration-of-breast-cancer-cells
#3
Emad Heidary Arash, Ahmed Shiban, Siyuan Song, Liliana Attisano
The Hippo pathway is a critical regulator of tissue size, and aberrations in pathway regulation lead to cancer. MST1/2 and LATS1/2 kinases comprise the core of the pathway that, in association with adaptor proteins SAV and MOB, functions in a sequential manner to phosphorylate and inhibit the transcription factors YAP and TAZ. Here we identify mammalian MARK family members as activators of YAP/TAZ. We show that depletion of MARK4 in MDA-MB-231 breast cancer cells results in the loss of nuclear YAP/TAZ and decreases the expression of YAP/TAZ targets...
February 9, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28177901/s100a7-promotes-lung-adenocarcinoma-to-squamous-carcinoma-transdifferentiation-and-its-expression-is-differentially-regulated-by-the-hippo-yap-pathway-in-lung-cancer-cells
#4
Rui Wang, Yunguang Li, Enze Hu, Fei Kong, Junhao Wang, Jin Liu, Qirui Shao, Ying Hao, Dacheng He, Xueyuan Xiao
Our previous study revealed that S100A7 was selectively expressed in lung squamous cell carcinoma tissues but not in adenocarcinoma. Thus far, the functions of S100A7 in lung cancer have remained largely unknown. Here, we reveal that S100A7 overexpression facilitates the transdifferentiation from adenocarcinoma (ADC) to squamous carcinoma (SCC) in several lung cancer cells, which is confirmed by an increase in DNp63 expression and a decrease in thyroid transcription factor 1 (TTF1) and aspartic proteinase napsin (napsin A) expression...
February 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28174264/hippo-signaling-promotes-jnk-dependent-cell-migration
#5
Xianjue Ma, Hongxiang Wang, Jiansong Ji, Wenyan Xu, Yihao Sun, Wenzhe Li, Xiaoping Zhang, Juxiang Chen, Lei Xue
Overwhelming studies show that dysregulation of the Hippo pathway is positively correlated with cell proliferation, growth, and tumorigenesis. Paradoxically, the detailed molecular roles of the Hippo pathway in cell invasion remain debatable. Using a Drosophila invasion model in wing epithelium, we show herein that activated Hippo signaling promotes cell invasion and epithelial-mesenchymal transition through JNK, as inhibition of JNK signaling dramatically blocked Hippo pathway activation-induced matrix metalloproteinase 1 expression and cell invasion...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28169360/loss-of-dlg5-promotes-breast-cancer-malignancy-by-inhibiting-the-hippo-signaling-pathway
#6
Jie Liu, Juan Li, Pingping Li, Yaochun Wang, Zheyong Liang, Yina Jiang, Jing Li, Chen Feng, Ruiqi Wang, He Chen, Can Zhou, Jianmin Zhang, Jin Yang, Peijun Liu
Discs Large Homolog 5 (DLG5) plays an important role in the maintenance of epithelial cell polarity. Recent research showed that DLG5 is decreased in Yes-associated protein (YAP)-overexpressing cells. However, the exact relationship between DLG5 and YAP is not clear. In this study, we showed that loss of DLG5 promoted breast cancer cell proliferation by inhibiting the Hippo signaling pathway and increasing nuclear YAP expression. Furthermore, depletion of DLG5 induced epithelial-mesenchymal transition (EMT) and disrupted epithelial cell polarity, which was associated with altered expression of Scribble, ZO1, E-cadherin and N-cadherin and their mislocalization...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28165342/epicardial-yap-taz-orchestrate-an-immunosuppressive-response-following-myocardial-infarction
#7
Vimal Ramjee, Deqiang Li, Lauren J Manderfield, Feiyan Liu, Kurt A Engleka, Haig Aghajanian, Christopher B Rodell, Wen Lu, Vivienne Ho, Tao Wang, Li Li, Anamika Singh, Dasan M Cibi, Jason A Burdick, Manvendra K Singh, Rajan Jain, Jonathan A Epstein
Ischemic heart disease resulting from myocardial infarction (MI) is the most prevalent form of heart disease in the United States. Post-MI cardiac remodeling is a multifaceted process that includes activation of fibroblasts and a complex immune response. T-regulatory cells (Tregs), a subset of CD4+ T cells, have been shown to suppress the innate and adaptive immune response and limit deleterious remodeling following myocardial injury. However, the mechanisms by which injured myocardium recruits suppressive immune cells remain largely unknown...
February 6, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28154141/the-nonreceptor-tyrosine-kinase-c-src-attenuates-scf-%C3%AE-trcp-e3-ligase-activity-abrogating-taz-proteasomal-degradation
#8
Matan Shanzer, Julia Adler, Inna Ricardo-Lax, Nina Reuven, Yosef Shaul
The polyomavirus middle T antigen (PyMT) oncogene activates the cellular nonreceptor tyrosine kinase c-Src and recruits the Hippo pathway effectors, Yap (yes-associated protein) and Taz (transcriptional coactivator with PDZ-binding motif), as key steps in oncogenesis. Yap and Taz are transcription coactivators shuttling from the cytoplasm to the nucleus. The Hippo pathway kinase Lats1/2 (large tumor suppressor homolog) reduces Yap/Taz nuclear localization and minimizes their cytoplasmic levels by facilitating their ubiquitination by the E3 ligase SCF(β-TrCP)...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28152516/tnfaip8-interacts-with-lats1-and-promotes-aggressiveness-through-regulation-of-hippo-pathway-in-hepatocellular-carcinoma
#9
Qianze Dong, Lin Fu, Yue Zhao, Chengyao Xie, Qingchang Li, Enhua Wang
Although TNFAIP8 overexpression has been implicated in several human cancers, its clinical significance and biological function in hepatocellular carcinoma (HCC) remains unknown. Our study demonstrated that TNFAIP8 overexpression in primary HCC samples correlated with TNM stage, recurrence, poor prognosis and served as an independent favorable prognostic factor. We further showed that TNFAIP8 upregulated cell proliferation, migration, invasion and xenograft tumor growth of HCC cells. In addition, TNFAIP8 overexpression inhibited YAP phosphorylation, increased its nuclear localization and stabilization, leading to upregulation of cyclin proteins, CTGF and cell proliferation...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28150487/structural-insights-into-the-regulation-of-hippo-signaling
#10
Leah Cairns, Thao Tran, Jennifer M Kavran
During development, the Hippo pathway regulates the balance between cell proliferation and apoptosis to control organ size. Appropriate Hippo signaling is associated with stem cell maintenance, while inappropriate signaling can result in tumorigenesis and cancer. Cellular and genetic investigations have identified core components and determined that complex formation and protein phosphorylation are crucial regulatory events. The recent spate of high-resolution structures of Hippo pathway components have begun to reveal the molecular mechanisms controlling these events, including the molecular determinates of complex formation between YAP and TEAD, the role of phosphorylation in controlling complex formation by Mob, and the conformational changes accompanying Mst1/2 kinase domain activation...
February 9, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28149906/targeting-nf2-hippo-yap-signaling-pathway-for-cardioprotection-after-ischemia-reperfusion-injury
#11
COMMENT
Masum M Mia, Ayshwarya L Chelakkot-Govindalayathil, Manvendra K Singh
No abstract text is available yet for this article.
December 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28139652/lnc-ing-ror1-her3-and-hippo-signalling-in-metastasis
#12
Wei Zhuo, Yibin Kang
Long noncoding RNAs (lncRNAs) are increasingly recognized for their role in cancer progression. The previously uncharacterized lncRNA MAYA is now shown to promote bone metastasis by bridging ROR1-HER3 and Hippo-YAP pathways. Neuregulin-induced HER3 phosphorylation by ROR1 recruits a MAYA-containing protein complex to methylate Hippo/MST1 and activate YAP target genes that are essential for bone metastasis.
January 31, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28137778/merlin-controls-the-repair-capacity-of-schwann-cells-after-injury-by-regulating-hippo-yap-activity
#13
Thomas Mindos, Xin-Peng Dun, Katherine North, Robin D S Doddrell, Alexander Schulz, Philip Edwards, James Russell, Bethany Gray, Sheridan L Roberts, Aditya Shivane, Georgina Mortimer, Melissa Pirie, Nailing Zhang, Duojia Pan, Helen Morrison, David B Parkinson
Loss of the Merlin tumor suppressor and activation of the Hippo signaling pathway play major roles in the control of cell proliferation and tumorigenesis. We have identified completely novel roles for Merlin and the Hippo pathway effector Yes-associated protein (YAP) in the control of Schwann cell (SC) plasticity and peripheral nerve repair after injury. Injury to the peripheral nervous system (PNS) causes a dramatic shift in SC molecular phenotype and the generation of repair-competent SCs, which direct functional repair...
February 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28130761/the-hippo-pathway-in-tissue-homeostasis-and-regeneration
#14
REVIEW
Yu Wang, Aijuan Yu, Fa-Xing Yu
While several organs in mammals retain partial regenerative capability following tissue damage, the underlying mechanisms remain unclear. Recently, the Hippo signaling pathway, better known for its function in organ size control, has been shown to play a pivotal role in regulating tissue homeostasis and regeneration. Upon tissue injury, the activity of YAP, the major effector of the Hippo pathway, is transiently induced, which in turn promotes expansion of tissue-resident progenitors and facilitates tissue regeneration...
January 27, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28114269/a-ror1-her3-lncrna-signalling-axis-modulates-the-hippo-yap-pathway-to-regulate-bone-metastasis
#15
Chunlai Li, Shouyu Wang, Zhen Xing, Aifu Lin, Ke Liang, Jian Song, Qingsong Hu, Jun Yao, Zhongyuan Chen, Peter K Park, David H Hawke, Jianwei Zhou, Yan Zhou, Shuxing Zhang, Han Liang, Mien-Chie Hung, Gary E Gallick, Leng Han, Chunru Lin, Liuqing Yang
Bone metastases remain a serious health concern because of limited therapeutic options. Here, we report that crosstalk between ROR1-HER3 and the Hippo-YAP pathway promotes breast cancer bone metastasis in a long noncoding RNA-dependent fashion. Mechanistically, the orphan receptor tyrosine kinase ROR1 phosphorylates HER3 at a previously unidentified site Tyr1307, following neuregulin stimulation, independently of other ErbB family members. p-HER3 Tyr1307 recruits the LLGL2-MAYA-NSUN6 RNA-protein complex to methylate Hippo/MST1 at Lys59...
January 23, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28112996/snail-slug-yap-taz-complexes-cooperatively-regulate-mesenchymal-stem-cell-function-and-bone-formation
#16
Yi Tang, Stephen J Weiss
Snail and Slug are zinc-finger transcription factors that play key roles in directing the epithelial-mesenchymal transition (EMT) programs associated with normal development as well as disease progression. More recent work suggests that these EMT-associated transcription factors also modulate the function of both embryonic and adult stem cells. Interestingly, YAP and TAZ, the co-transcriptional effectors of the Hippo pathway, likewise play an important role in stem cell self-renewal and lineage commitment. While direct intersections between the Snail/Slug and Hippo pathways have not been described previously, we recently described an unexpected cooperative interaction between Snail/Slug and YAP/TAZ that controls the self-renewal and differentiation properties of bone marrow-derived mesenchymal stem cells (MSCs), a cell population critical to bone development...
January 23, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28103766/long-term-exposure-to-imatinib-mesylate-downregulates-hippo-pathway-and-activates-yap-in-a-model-of-chronic-myelogenous-leukemia
#17
Anna Chorzalska, Javier Flores Kim, Karim Roder, Alexander Tepper, Nagib Ahsan, R Shyama Prasad Rao, Adam J Olszewski, Xiaoqing Yu, Dmitry Terentyev, John Morgan, Diana O Treaba, Ting Zhao, Olin Liang, Philip Gruppuso, Patrycja Dubielecka
Despite the success of tyrosine kinase inhibitor (TKI) therapy in chronic myelogenous leukemia (CML), leukemic stem/progenitor cells remain detectable even in the state of deep molecular remission. Mechanisms that allow them to persist despite continued kinase inhibition remain unclear. We have previously shown that prolonged exposure to imatinib mesylate results in dysregulation of Akt/Erk 1/2 signaling, upregulation of miR-181a, enhanced adhesiveness, and resistance to high imatinib mesylate. In order to characterize the molecular basis and reversibility of those effects, we applied gene and protein expression analysis, quantitative phosphoproteomic, and direct miR-181a inhibition to our cellular model of CML cells subjected to prolonged exposure to imatinib mesylate...
January 19, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28102225/glucocorticoid-receptor-signalling-activates-yap-in-breast-cancer
#18
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
#19
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
#20
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...
March 2017: Biomaterials
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