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Yap hippo

Erika Ishihara, Hiroshi Nishina
The vertebrate body shape is formed by the specific sizes and shapes of its resident tissues and organs, whose alignments are essential for proper functioning. To maintain tissue and organ shape, and thereby function, it is necessary to remove senescent, transformed, and/or damaged cells, which impair function and can lead to tumorigenesis. However, the molecular mechanisms underlying three-dimensional (3D) organ formation and homeostasis are not fully clear. Yes-associated protein (YAP) is a transcriptional co-activator that is involved in organ size control and tumorigenesis...
April 17, 2018: Cancers
Thanh Hung Nguyen, Jan-Michael Kugler
The Hippo pathway serves as a key barrier for oncogenic transformation. It acts by limiting the activity of the proto-oncogenes YAP and TAZ. Reduced Hippo signaling and elevated YAP/TAZ activities are frequently observed in various types of tumors. Emerging evidence suggests that the ubiquitin system plays an important role in regulating Hippo pathway activity. Deregulation of ubiquitin ligases and of deubiquitinating enzymes has been implicated in increased YAP/TAZ activity in cancer. In this article, we review recent insights into the ubiquitin-mediated regulation of the mammalian Hippo pathway, its deregulation in cancer, and possibilities for targeting the Hippo pathway through the ubiquitin system...
April 17, 2018: Cancers
Huan Liu, Xiaoming Dai, Xiaolei Cao, Huan Yan, Xinyan Ji, Haitao Zhang, Shuying Shen, Yuan Si, Hailong Zhang, Jianfeng Chen, Li Li, Jonathan C Zhao, Jindan Yu, Xin-Hua Feng, Bin Zhao
Yes-associated protein (YAP) is a transcriptional co-activator and a major effector of the Hippo pathway that promotes cell proliferation and stemness, while inhibiting apoptosis. YAP plays a central role in organ size control, and its deregulation strongly promotes cancer initiation and progression. However, the mechanisms by which YAP promotes cell invasion and metastasis are not fully understood. Here, we report that YAP induces leukocyte-specific integrin β2 ( ITGB2 ) expression in cancer cells, thereby promoting cell invasion through the endothelium in a manner mimicking leukocytes...
April 17, 2018: EMBO Reports
Kyeong Hwan Moon, Jin Woo Kim
Vertebrate organ development is accompanied by demarcation of tissue compartments, which grow coordinately with their neighbors. Hence, perturbing the coordinative growth of neighboring tissue compartments frequently results in organ malformation. The growth of tissue compartments is regulated by multiple intercellular and intracellular signaling pathways, including the Hippo signaling pathway that limits the growth of various organs. In the optic neuroepithelial continuum, which is partitioned into the retina, retinal pigment epithelium (RPE) and ciliary margin (CM) during eye development, the Hippo signaling activity operates differentially, as it does in many tissues...
April 11, 2018: Molecules and Cells
Lang Li, Liang Dong, Jiaojie Hui, Fei Gao, Qiuhui Wang, Lan Yang, Jiangqian Zhang, Jie Yan
OBJECTIVE: To explore the effects of Hippo signaling on anti-oxidative stress of mouse marrow mesenchymal stem cells (mMSCs) in vitro. METHODS: mMSCs derived from C57BL/6 mice were identified using fluorescence-activated cell sorting analysis and the capabilities of osteogenic, chondrogenic and adipogenic differentiation were evaluated. 2-deoxy-D-glucose (2-DG) or XMU-MP-1 was used to modulate Hippo signaling. Oxidative stress was induced by H2 O2 treatment and the effect of oxidative stress induced by H2 O2 on survival of mMSCs was evaluated using methyl thiazolyl tetrazolium (MTT) assay...
April 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Giulia Santinon, Irene Brian, Arianna Pocaterra, Patrizia Romani, Elisa Franzolin, Chiara Rampazzo, Silvio Bicciato, Sirio Dupont
YAP/TAZ, downstream transducers of the Hippo pathway, are powerful regulators of cancer growth. How these factors control proliferation remains poorly defined. Here, we found that YAP/TAZ directly regulate expression of key enzymes involved in deoxynucleotide biosynthesis and maintain dNTP precursor pools in human cancer cells. Regulation of deoxynucleotide metabolism is required for YAP-induced cell growth and underlies the resistance of YAP-addicted cells to chemotherapeutics targeting dNTP synthesis. During RAS-induced senescence, YAP/TAZ bypass RAS-mediated inhibition of nucleotide metabolism and control senescence...
April 12, 2018: EMBO Journal
Xiaoguang Zhao, Jian Sun, Wei Su, Huitong Shan, Bowen Zhang, Yining Wang, Azaliia Shabanova, Hongli Shan, Haihai Liang
Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrotic interstitial pneumonia with high mortality. Melatonin, a hormone predominantly secreted by the pineal gland, has been reported to participate in the process of IPF. However, the mechanisms underlying the effect of melatonin in pulmonary fibrosis have not been elucidated to date. This study was designed to evaluate the anti-fibrotic role of melatonin in pulmonary fibrosis and to elucidate the potential mechanisms. We observed that melatonin markedly attenuated bleomycin (BLM)-induced experimental lung fibrosis in mice and inhibited TGF-β1-induced fibrogenesis in lung fibroblasts...
April 9, 2018: International Journal of Molecular Sciences
Jaimee E Hoefert, Glen A Bjerke, Dongmei Wang, Rui Yi
The microRNA (miRNA)-200 (miR-200) family is highly expressed in epithelial cells and frequently lost in metastatic cancer. Despite intensive studies into their roles in cancer, their targets and functions in normal epithelial tissues remain unclear. Importantly, it remains unclear how the two subfamilies of the five-miRNA family, distinguished by a single nucleotide within the seed region, regulate their targets. By directly ligating miRNAs to their targeted mRNA regions, we identify numerous miR-200 targets involved in the regulation of focal adhesion, actin cytoskeleton, cell cycle, and Hippo/Yap signaling...
March 30, 2018: Journal of Cell Biology
Ramón García-Escudero, Carmen Segrelles, Marta Dueñas, María Pombo, Claudio Ballestín, Marina Alonso-Riaño, Pablo Nenclares, Roberto Álvarez-Rodríguez, Gregorio Sánchez-Aniceto, Ana Ruíz-Alonso, José Luis López-Cedrún, Jesús M Paramio, Corina Lorz
OBJECTIVES: Phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) is commonly altered in many human tumors, leading to the activation of p110α enzymatic activity that stimulates growth factor-independent cell growth. PIK3CA alterations such as mutation, gene amplification and overexpression are common in head and neck squamous cell carcinoma (HNSCC) and. We aim to explore how these alterations and clinical outcome are associated, as well as the molecular mechanisms involved...
April 2018: Oral Oncology
Zaid Taha, Helena J Janse van Rensburg, Xiaolong Yang
Since its discovery, the Hippo pathway has emerged as a central signaling network in mammalian cells. Canonical signaling through the Hippo pathway core components (MST1/2, LATS1/2, YAP and TAZ) is important for development and tissue homeostasis while aberrant signaling through the Hippo pathway has been implicated in multiple pathologies, including cancer. Recent studies have uncovered new roles for the Hippo pathway in immunology. In this review, we summarize the mechanisms by which Hippo signaling in pathogen-infected or neoplastic cells affects the activities of immune cells that respond to these threats...
March 28, 2018: Cancers
Atif A Ahmed, Sultan S Habeebu, Ashley K Sherman, Shui Q Ye, Nicole Wood, Katherine M Chastain, Maria G Tsokos
Rhabdomyosarcoma (RMS) is a common malignancy of soft tissue, subclassified as alveolar (ARMS), pleomorphic (PRMS), spindle cell/sclerosing (SRMS), and embryonal (ERMS) types. The Yes-associated protein (YAP) is a member of the Hippo pathway and a transcriptional regulator that controls cell proliferation. We have studied the immunohistochemical expression of YAP in different RMSs, arranged in tissue microarray (TMA) and whole slide formats. Pertinent clinical data including patient age, gender, tumor location, and clinical stage were collected...
March 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
Matthijs Steven Ruiter, Maurizio Pesce
Autologous saphenous veins are the most commonly used conduits in revascularization of the ischemic heart by coronary artery bypass graft surgery, but are subject to vein graft failure. The current mini review aims to provide an overview of the role of mechanotransduction signalling underlying vein graft failure to further our understanding of the disease progression and to improve future clinical treatment. Firstly, limitation of damage during vein harvest and engraftment can improve outcome. In addition, cell cycle inhibition, stimulation of Nur77 and external grafting could form interesting therapeutic options...
2018: Frontiers in Cardiovascular Medicine
Zhengdong Jiang, Cancan Zhou, Liang Cheng, Bin Yan, Ke Chen, Xin Chen, Liang Zong, Jianjun Lei, Wanxing Duan, Qinhong Xu, Xuqi Li, Zheng Wang, Qingyong Ma, Jiguang Ma
BACKGROUND: Hippo/YAP pathway is known to be important for development, growth and organogenesis, and dysregulation of this pathway leads to tumor progression. We and others find that YAP is up-regulated in pancreatic ductal adenocarcinoma (PDAC) and associated with worse prognosis of patients. Activated pancreatic stellate cells (PSCs) forming the components of microenvironment that enhance pancreatic cancer cells (PCs) invasiveness and malignance. However, the role and mechanism of YAP in PDAC tumor-stromal interaction is largely unknown...
March 27, 2018: Journal of Experimental & Clinical Cancer Research: CR
Madhura Kulkarni, Tuan Zea Tan, Nurfarhanah Bte Syed Sulaiman, John M Lamar, Prashali Bansal, Jianzhou Cui, Yiting Qiao, Yoshiaki Ito
Hippo pathway target, YAP has emerged as an important player in solid tumor progression. Here, we identify RUNX1 and RUNX3 as novel negative regulators of oncogenic function of YAP in the context of breast cancer. RUNX proteins are one of the first transcription factors identified to interact with YAP. RUNX1 or RUNX3 expression abrogates YAP-mediated pro-tumorigenic properties of mammary epithelial cell lines in an interaction dependent manner. RUNX1 and RUNX3 inhibit YAP-mediated migration and stem-ness properties of mammary epithelial cell lines by co-regulating YAP-mediated gene expression...
March 6, 2018: Oncotarget
Yuhua Xue, Wendy M Mars, William Bowen, Aatur D Singhi, John Stoops, George K Michalopoulos
Glypican 3 (GPC3) is over-expressed in hepatocellular carcinomas (HCC). GPC3 binds to CD81. Forced expression of CD81 in a GPC3 expressing HCC cell line caused activation of Hippo, decrease in Ezrin phosphorylation, and decrease in Yap. CD81 is also associated with HCV entry into hepatocytes. Activation of CD81 by agonistic antibody causes activation of spleen kinase (Syk) and phosphorylation of Ezrin, a regulator of Hippo pathway. In cultures of normal hepatocytes, CD81 agonistic antibody led to enhanced phosphorylation of Ezrin and increase in nuclear Yap...
March 22, 2018: American Journal of Pathology
Wenyi Zhou, Mingyi Zhao
Cardiovascular disease remains the leading cause of death around the globe. Cardiac deterioration is associated with irreversible cardiomyocyte loss. Understanding how the cardiovascular system develops and the pathological processes of cardiac disease will contribute to finding novel and preventive therapeutic methods. The canonical Hippo tumor suppressor pathway in mammalian cells is primarily composed of the MST1/2-SAV1-LATS1/2-MOB1-YAP/TAZ cascade. Continuing research on this pathway has identified other factors like RASSF1A, Nf2, MAP4Ks, and NDR1/2, further enriching our knowledge of the Hippo-YAP pathway...
2018: Journal of Immunology Research
Ping-Chih Hsu, Jinbai Miao, Yu-Cheng Wang, Wen-Qian Zhang, Yi-Lin Yang, Chih-Wei Wang, Cheng-Ta Yang, Zhen Huang, Joanna You, Zhidong Xu, David M Jablons, Liang You
Although tumour PD-L1 (CD274) expression had been used as a predictive biomarker in checkpoint immunotherapy targeting the PD1/PD-L1 axis in various cancers, the regulation of PD-L1 (CD274) expression is unclear. Yes-associated protein (YAP), an important oncogenic protein in Hippo signalling pathway, reportedly promotes cancer development. We investigated whether inhibition of YAP down-regulates PD-L1 (CD274) in human malignant pleural mesothelioma (MPM). Western blotting showed that 2 human MPM cell lines (H2052 and 211H) had increased PD-L1 protein expression compared to H290, MS-1 and H28 cells...
March 24, 2018: Journal of Cellular and Molecular Medicine
Ping-Chih Hsu, Jinbai Miao, Zhen Huang, Yi-Lin Yang, Zhidong Xu, Joanna You, Yuyuan Dai, Che-Chung Yeh, Geraldine Chan, Shu Liu, Anatoly Urisman, Cheng-Ta Yang, David M Jablons, Liang You
Yes-associated protein (YAP) is a main mediator of the Hippo pathway and promotes cancer development and progression in human lung cancer. We sought to determine whether inhibition of YAP suppresses metastasis of human lung adenocarcinoma in a murine model. We found that metastatic NSCLC cell lines H2030-BrM3(K-rasG12C mutation) and PC9-BrM3 (EGFRΔexon19 mutation) had a significantly decreased p-YAP(S127)/YAP ratio compared to parental H2030 (K-rasG12C mutation) and PC9 (EGFRΔexon19 mutation) cells (P < ...
March 24, 2018: Journal of Cellular and Molecular Medicine
Benji Lv, Lianhai Zhang, Runchen Miao, Xiaohong Xiang, Shunbin Dong, Ting Lin, Ke Li, Qu Kai
Hepatoblastoma (HB), as a common pediatric liver malignancy, is composed of a variety of subgroups with different clinical outcomes. Long-noncoding RNA (lncRNA) has crucial roles in cancer biology. However, the association between lncRNA and HB has not been fully investigated. In this study, we screened lncRNA expression profiles that were annotated from the GSE75271 dataset. A total of 225 differentially expressed lncRNAs (DELs) were identified based on comparison between three prognostic subgroups, and seven of them (XR_241302, XR_923061, NR_038322, XR_951687, XR_934593, NR_120317 and XR_93406) that exhibited highly predictive accuracies were selected for functional analysis...
February 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Xuesong Yuan, Wenfeng Wei, Qing Bao, Hongchun Chen, Peng Jin, Wenqing Jiang
This work aims to study the roles and mechanisms of metformin in glioma cells stemness and epithelial-mesenchymal transition. Here, we found that metformin suppressed glioma cells spheroid formation and size, inhibited the expression of glioma stemness-related marker, CD133. Additionally, Metformin attenuated TGF-β-induced epithelial-mesenchymal transition in glioma cells. Mechanistically, metformin inhibited the nuclear abundance of YAP, a key effector of Hippo pathway, subsequently leading to its cytoplasmic retention, and thus reduced YAP transcriptional modulating activity...
March 19, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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