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https://www.readbyqxmd.com/read/29222344/trip6-inhibits-hippo-signaling-in-response-to-tension-at-adherens-junctions
#1
Shubham Dutta, Sebastian Mana-Capelli, Murugan Paramasivam, Ishani Dasgupta, Heather Cirka, Kris Billiar, Dannel McCollum
The transcriptional co-activator YAP controls cell proliferation, survival, and tissue regeneration in response to changes in the mechanical environment. It is not known how mechanical stimuli such as tension are sensed and how the signal is transduced to control YAP activity. Here, we show that the LIM domain protein TRIP6 acts as part of a mechanotransduction pathway at adherens junctions to promote YAP activity by inhibiting the LATS1/2 kinases. Previous studies showed that vinculin at adherens junctions becomes activated by mechanical tension...
December 8, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29219182/the-emerging-role-of-hippo-signaling-pathway-in-regulating-osteoclast-formation
#2
REVIEW
Wanlei Yang, Weiqi Han, An Qin, Ziyi Wang, Jiake Xu, Yu Qian
A delicate balance between osteoblastic bone formation and osteoclastic bone resorption is crucial for bone homeostasis. This process is regulated by the Hippo signaling pathway including key regulatory molecules RASSF2, NF2, MST1/2, SAV1, LATS1/2, MOB1, YAP and TAZ. It is well established that the Hippo signaling pathway plays an important part in regulating osteoblast differentiation, but its role in osteoclast formation and activation remains poorly understood. In this review, we discuss the emerging role of Hippo-signaling pathway in osteoclast formation and bone homeostasis...
December 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29217192/amot-is-required-for-yap-function-in-high-glucose-induced-liver-malignancy
#3
Ya Liu, Zhicheng Lu, Yi Shi, Fenyong Sun
AMOT has been identified as a YAP interactor. However, how AMOT regulates YAP remains unclear and controversy. Here, we identified that besides YAP, AMOT was another Hippo signaling core factor which could be O-GlcNAcylated. Moreover, high glucose (HG) was able to enhance the expression and O-GlcNAcylation of AMOT. We also found that HG stimulated nuclear accumulation, transcription activity, interaction with transcription factor and transcription of target genes of YAP via AMOT, while AMOT acted as a suppressor of YAP in normal glucose level...
December 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29215734/study-on-mechanism-about-long-noncoding-rna-malat1-affecting-pancreatic-cancer-by-regulating-hippo-yap-signaling
#4
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/29214772/pseudolaric-acid-b-inhibits-proliferation-invasion-and-epithelial-to-mesenchymal-transition-in-human-pancreatic-cancer-cell
#5
Xiaoyu Li, Xianzhi Zhao, Wen Song, Zibin Tian, Lin Yang, Qinghui Niu, Qi Zhang, Man Xie, Bin Zhou, Yonghong Xu, Jun Wu, Cuiping Zhang
PURPOSE: This study was aimed to investigate the effect of pseudolaric acid B (PAB) on proliferation, invasion and epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cells and to explore the possible mechanism. MATERIALS AND METHODS: The pancreatic cancer cell line SW1990 was cultured and treated with PAB dose- and time-dependent manners. Cell proliferation and invasion ability were measured by MTT assay and Matrigel/Transwell test, respectively. Semi-quantitative real-time polymerase chain reaction and Western blotting were conducted to detect the expression of EMT markers and the key molecules...
January 2018: Yonsei Medical Journal
https://www.readbyqxmd.com/read/29207260/a-balance-of-yki-sd-activator-and-e2f1-sd-repressor-complexes-controls-cell-survival-and-affects-organ-size
#6
Peng Zhang, Chunli Pei, Xi Wang, Jinyi Xiang, Bao-Fa Sun, Yongsheng Cheng, Xiaolong Qi, Marco Marchetti, Jia-Wei Xu, Ying-Pu Sun, Bruce A Edgar, Zengqiang Yuan
The Hippo/Yki and RB/E2F pathways both regulate tissue growth by affecting cell proliferation and survival, but interactions between these parallel control systems are poorly defined. In this study, we demonstrate that interaction between Drosophila E2F1 and Sd disrupts Yki/Sd complex formation and thereby suppresses Yki target gene expression. RBF modifies these effects by reducing E2F1/Sd interaction. This regulation has significant effects on apoptosis, organ size, and progenitor cell proliferation. Using a combination of DamID-seq and RNA-seq, we identified a set of Yki targets that play a diversity of roles during development and are suppressed by E2F1...
December 4, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29193599/characterization-of-mice-carrying-a-conditional-tead1-allele
#7
Tong Wen, Qin Yin, Luyi Yu, Guoqing Hu, Jinhua Liu, Wei Zhang, Liang Huang, Huabo Su, Menghong Wang, Jiliang Zhou
The Hippo-YAP pathway is essential for controlling organ size and tumorigenesis. Previous studies have demonstrated that the primary outcome of YAP signaling in the nucleus is achieved by interaction with the transcription factor TEAD1. The YAP/TEAD1 complex binds to DNA element and regulates the expression of genes involved in cell growth. However, constitutive knockout of TEAD1 leads to early embryonic lethality in mice. Thus, generation of a floxed TEAD1 mouse becomes crucial for further understanding mid- to late-gestation and post-natal role of TEAD1...
November 30, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/29185453/dysregulation-of-yap-by-arf-stimulated-with-tea-derived-carbon-nanodots
#8
Yingqiu Xie, Qinglei Sun, Ayan A Nurkesh, Jiang Lu, Sholpan Kauanova, Jinhong Feng, Darkhan Tursynkhan, Qing Yang, Aishabibi Kassymbek, Mirat Karibayev, Korlan Duisenova, Haiyan Fan, Xiao Wang, Limara Manarbek, Aisulu Maipas, Zhenbang Chen, Mannix P Balanay
YAP is a downstream nuclear transcription factor of Hippo pathway which plays an essential role in development, cell growth, organ size and homeostasis. It was previously identified that elevation of YAP in genomics of genetic engineered mouse (GEM) model of prostate cancer is associated with Pten/Trp53 inactivation and ARF elevation hypothesizing the essential crosstalk of AKT/mTOR/YAP with ARF in prostate cancer. However, the detailed function and trafficking of YAP in cancer cells remains unclear. Using GEM microarray model, we found ARF dysregulates Hippo and Wnt pathways...
November 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29183995/deubiquitylase-usp9x-suppresses-tumorigenesis-by-stabilizing-large-tumor-suppressor-kinase-2-lats2-in-the-hippo-pathway
#9
Chu Zhu, Xinyan Ji, Haitao Zhang, Qi Zhou, Xiaolei Cao, Mei Tang, Yuan Si, Huan Yan, Li Li, Tingbo Liang, Xin-Hua Feng, Bin Zhao
The Hippo pathway plays important roles in controlling organ size and in suppressing tumorigenesis through large tumor suppressor kinase 1/2 (LATS1/2)-mediated phosphorylation of YAP/TAZ transcription co-activators. The kinase activity of LATS1/2 is regulated by phosphorylation in response to extracellular signals. Moreover, LATS2 protein levels are repressed by the ubiquitin-proteasome system in conditions such as hypoxia. However, the mechanism that removes the ubiquitin modification from LATS2 and thereby stabilizes the protein is not well understood...
November 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29177764/rock-and-rho-playlist-for-preimplantation-development-streaming-to-hippo-pathway-and-apicobasal-polarity-in-the-first-cell-differentiation
#10
Vernadeth B Alarcon, Yusuke Marikawa
In placental mammalian development, the first cell differentiation produces two distinct lineages that emerge according to their position within the embryo: the trophectoderm (TE, placenta precursor) differentiates in the surface, while the inner cell mass (ICM, fetal body precursor) forms inside. Here, we discuss how such position-dependent lineage specifications are regulated by the RHOA subfamily of small GTPases and RHO-associated coiled-coil kinases (ROCK). Recent studies in mouse show that activities of RHO/ROCK are required to promote TE differentiation and to concomitantly suppress ICM formation...
2018: Advances in Anatomy, Embryology, and Cell Biology
https://www.readbyqxmd.com/read/29165358/understanding-the-molecular-genetics-of-basal-cell-carcinoma
#11
REVIEW
Cristina Pellegrini, Maria Giovanna Maturo, Lucia Di Nardo, Valeria Ciciarelli, Carlota Gutiérrez García-Rodrigo, Maria Concetta Fargnoli
Basal cell carcinoma (BCC) is the most common human cancer and represents a growing public health care problem. Several tumor suppressor genes and proto-oncogenes have been implicated in BCC pathogenesis, including the key components of the Hedgehog pathway, PTCH1 and SMO, the TP53 tumor suppressor, and members of the RAS proto-oncogene family. Aberrant activation of the Hedgehog pathway represents the molecular driver in basal cell carcinoma pathogenesis, with the majority of BCCs carrying somatic point mutations, mainly ultraviolet (UV)-induced, and/or copy-loss of heterozygosis in the PTCH1 gene...
November 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29162747/therapeutic-effect-of-a-novel-wnt-pathway-inhibitor-on-cardiac-regeneration-after-myocardial-infarction
#12
Chunyu Zeng, Dezhong Yang, Wenbin Fu, Liangpeng Li, Xuewei Xia, Qiao Liao, Rongchuan Yue, Hongmei Chen, Xiongwen Chen, Songzhu An, Wei Eric Wang
After myocardial infarction (MI), the heart is difficult to repair because of great loss of cardiomyoctyes and lack of cardiac regeneration. Novel drug candidates that aim at reducing pathological remodeling and stimulating cardiac regeneration are highly desirable. In this study, we identified if and how a novel porcupine inhibitor CGX1321 influenced MI and cardiac regeneration. Permanent ligation of left anterior descending (LAD) coronary artery was performed in mice to induce MI injury. Cardiac function was measured by echocardiography, infarct size was examined by TTC staining...
November 21, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29158053/transforming-growth-factor-beta1-promotes-articular-cartilage-repair-through-canonical-smad-and-hippo-pathways-in-bone-mesenchymal-stem-cells
#13
Jun Ying, Pinger Wang, Shanxing Zhang, Taotao Xu, Lei Zhang, Rui Dong, Shibing Xu, Peijian Tong, Chengliang Wu, Hongting Jin
AIMS: Transforming growth factor-β1 (TGF-β1) is a chondrogenic factor and has been reported to be able to enhance chondrocyte differentiation from bone marrow mesenchymal stem cells (BMSCs). Here we investigate the molecular mechanism through which TGF-β1 chronically promotes the repair of cartilage defect and inhibit chondrocyte hypertrophy. MAIN METHODS: Animal models of full thickness cartilage defects were divided into three groups: model group, BMSCs group (treated with BMSCs/calcium alginate gel) and BMSCs+TGF-β1 group (treated with Lentivirus-TGF-β1-EGFP transduced BMSCs/calcium alginate gel)...
November 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/29156422/syndecan-1-in-mechanosensing-of-nanotopological-cues-in-engineered-materials
#14
Victoria Le, Jason Lee, Somali Chaterji, Adrianne Spencer, Yen-Liang Liu, Peter Kim, Hsin-Chih Yeh, Deok-Ho Kim, Aaron B Baker
The cells of the vascular system are highly sensitive to biophysical cues from their local cellular microenvironment. To engineer improved materials for vascular devices and delivery of cell therapies, a key challenge is to understand the mechanisms that cells use to sense biophysical cues from their environment. Syndecans are heparan sulfate proteoglycans (HSPGs) that consist of a protein core modified with heparan sulfate glycosaminoglycan chains. Due to their presence on the cell surface and their interaction with cytoskeletal and focal adhesion associated molecules, cell surface proteoglycans are well poised to serve as mechanosensors of the cellular microenvironment...
November 9, 2017: Biomaterials
https://www.readbyqxmd.com/read/29155585/allosteric-inhibitors-of-shp2-with-therapeutic-potential-for-cancer-treatment
#15
Jingjing Xie, Xiaojia Si, Shoulai Gu, Mingliang Wang, Jian Shen, Haoyan Li, Jian Shen, Dan Li, Yanjia Fang, Cong Liu, Jidong Zhu
SHP2, a cytoplasmic protein-tyrosine phosphatase encoded by the PTPN11 gene, is involved in multiple cell signaling processes including Ras/MAPK and Hippo/YAP pathways. SHP2 has been shown to contribute to the progression of a number of cancer types including leukemia, gastric and breast cancer. It also regulates T-cell activation by interacting with inhibitory immune checkpoint receptors such as the programmed cell death 1 (PD-1) and B- and T-lymphocyte attenuator (BTLA). Thus, SHP2 inhibitors have drawn great attention by both inhibiting tumor cell proliferation and activating T cell immune responses toward cancer cells...
November 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29155025/understanding-the-role-of-mammalian-sterile-20-like-kinase-1-mst1-in-cardiovascular-disorders
#16
REVIEW
Yang Yang, Haichang Wang, Zhiqiang Ma, Wei Hu, Dongdong Sun
Hippo signaling is a conserved pathway and plays important role in controlling cell proliferation and differentiation. As critical components of the Hippo pathway in mammals, mammalian sterile 20-like kinase 1 (MST1) participate in cell apoptosis and cell proliferation. Yes-associated protein (YAP) acts as a downstream transcriptional co-activator of MST1. MST1 is present in heart tissue and helps determine the fate of cardiomyocytes by regulating the balance between autophagy and apoptosis. Recent studies showed MST1 signaling is an essential participant in many cardiovascular disorders, including aortic dissection, aortic aneurysm, atherosclerosis, myocardial ischemic injury, and cardiomyopathy...
November 15, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29154888/activation-of-yap1-taz-signaling-in-ischemic-heart-disease-and-dilated-cardiomyopathy
#17
Ning Hou, Ying Wen, Xun Yuan, Haodong Xu, Xuejun Wang, Faqian Li, Bo Ye
Genetic manipulation of key components of the evolutionally conserved Hippo pathway has shown that the precise control of these signaling molecules is critical to cardiac development and response to stresses. However, how this pathway is involved in the progression of cardiac dysfunction in different heart diseases remains unclear. We investigated the expressional levels and subcellular localization of Yap1, Taz, and Tead1 and determined Hippo target gene expression in failing human hearts with ischemic heart disease (IHD) and idiopathic dilated cardiomyopathy (IDC) and mouse desmin-related cardiomyopathy (DES)...
November 15, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29154163/upstairs-downstairs-spatial-regulation-of-hippo-signalling
#18
REVIEW
Alexander Fulford, Nicolas Tapon, Paulo S Ribeiro
Cellular signalling lies at the heart of every decision involved in the development and homeostasis of multicellular organisms. The Hippo pathway was discovered nearly two decades ago through seminal work in Drosophila and rapidly emerged as a crucial signalling network implicated in developmental and oncogenic growth, tissue regeneration and stem cell biology. Here, we review recent advances in the field relating to the upstream regulation of Hippo signalling and the intracellular tug-of-war that tightly controls its main target, the transcriptional co-activator Yorkie/YAP...
November 17, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29149457/hmgb1-controls-liver-cancer-initiation-through-yap-dependent-aerobic-glycolysis
#19
Ruochan Chen, Shan Zhu, Xue-Gong Fan, Haichao Wang, Michael T Lotze, Herbert J Zeh, Timothy R Billiar, Rui Kang, Daolin Tang
Emerging studies have suggested that the Hippo pathway is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the key regulator of the Hippo pathway in liver tumor metabolic reprogramming remains elusive. Here, we provide evidence to support that high mobility group box 1 (HMGB1), a chromosomal protein, plays a role in the regulation of the Hippo pathway during liver tumorigenesis. Cre/loxP recombination-mediated HMGB1 depletion in hepatocytes blocks diethylnitrosamine-induced liver cancer initiation in mice, whereas shRNA-mediated gene silencing of HMGB1 inhibits HCC cell proliferation...
November 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29136529/yap-dependent-axl-overexpression-mediates-resistance-to-egfr-inhibitors-in-nsclc
#20
Elena Ghiso, Cristina Migliore, Vito Ciciriello, Elena Morando, Annalisa Petrelli, Simona Corso, Emmanuele De Luca, Gaia Gatti, Marco Volante, Silvia Giordano
The Yes-associated protein (YAP) is a transcriptional co-activator upregulating genes that promote cell growth and inhibit apoptosis. The main dysregulation of the Hippo pathway in tumors is due to YAP overexpression, promoting epithelial to mesenchymal transition, cell transformation, and increased metastatic ability. Moreover, it has recently been shown that YAP plays a role in sustaining resistance to targeted therapies as well. In our work, we evaluated the role of YAP in acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in lung cancer...
November 11, 2017: Neoplasia: An International Journal for Oncology Research
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