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https://www.readbyqxmd.com/read/28644436/the-lats1-and-lats2-tumor-suppressors-beyond-the-hippo-pathway
#1
REVIEW
Noa Furth, Yael Aylon
Proper cellular functionality and homeostasis are maintained by the convergent integration of various signaling cascades, which enable cells to respond to internal and external changes. The Dbf2-related kinases LATS1 and LATS2 (LATS) have emerged as central regulators of cell fate, by modulating the functions of numerous oncogenic or tumor suppressive effectors, including the canonical Hippo effectors YAP/TAZ, the Aurora mitotic kinase family, estrogen signaling and the tumor suppressive transcription factor p53...
June 23, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28637242/yap-and-wwtr1-regulate-the-expression-of-sex-determining-genes-in-sertoli-cells-but-their-inactivation-does-not-cause-sex-reversal
#2
Adrien Levasseur, Marilène Paquet, Derek Boerboom, Alexandre Boyer
Yes-associated protein (YAP) and WW containing transcription regulator 1 (WWTR1) are two functionally redundant transcriptional regulators that are downstream effectors of the Hippo signaling pathway, and that act as major regulators of cell growth and differentiation. To elucidate their role in Sertoli cells, primary Sertoli cell culture from Yapflox/flox; Wwtr1flox/flox animals were infected with a Cre recombinase-expressing adenovirus. Concomitant inactivation of Yap and Wwtr1 resulted in a decrease in the mRNA levels of the male sex differentiation genes Dhh, Dmrt1, Sox9 and Wt1, whereas those of genes involved in female differentiation (Wnt4, Rspo1 and Foxl2) were induced...
June 16, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28634071/the-novel-yap-target-gene-sgk1-upregulates-taz-activity-by-blocking-gsk3%C3%AE-mediated-taz-destabilization
#3
Geon Yoo, Tackhoon Kim, Chaeuk Chung, Deog-Su Hwang, Dae-Sik Lim
YAP (Yes-associated protein) and TAZ (transcription activator with PDZ binding motif) are important in tissue regeneration and cancer development, highlighting the importance of discovering partners that regulate their oncogenicity. SGK1 (serum/glucocorticoid regulated kinase 1), initially identified as a homolog of Akt in phosphoinositide 3-kinase signaling, acts as a serine/threonine protein kinase in multiple oncogenic pathways. However, possible links between SGK1 and Hippo-YAP/TAZ signaling remain unexplored...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28616573/yap-and-the-hippo-pathway-in-pediatric-cancer
#4
REVIEW
Atif A Ahmed, Abdalla D Mohamed, Melissa Gener, Weijie Li, Eugenio Taboada
The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell-cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis...
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/28611154/cytoresistance-after-acute-kidney-injury-is-limited-to-the-recovery-period-of-proximal-tubule-integrity-and-possibly-involves-hippo-yap-signaling
#5
Takamasa Iwakura, Yoshihide Fujigaki, Tomoyuki Fujikura, Takayuki Tsuji, Naro Ohashi, Akihiko Kato, Hideo Yasuda
Rat proximal tubule (PT) cells that have recovered from severe acute kidney injury induced by uranyl acetate (UA) develop cytoresistance to subsequent UA treatments. We reported that enhanced G1 arrest might contribute to cytoresistance. Herein, we examined these mechanisms by investigating Yes-associated protein (YAP), a regulator of cell number, and survivin, a downstream mediator of YAP that inhibits apoptosis. Rats pretreated with saline (vehicle group) or UA (AKI group) were injected with UA 2 weeks, 2 months, or 6 months after treatment...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28602051/yes-associated-protein-expression-is-correlated-to-the-differentiation-of-prostate-adenocarcinoma
#6
Myung-Giun Noh, Sung Sun Kim, Eu Chang Hwang, Dong Deuk Kwon, Chan Choi
Background: Yes-associated protein (YAP) in the Hippo signaling pathway is a growth control pathway that regulates cell proliferation and stem cell functions. Abnormal regulation of YAP was reported in human cancers including liver, lung, breast, skin, colon, and ovarian cancer. However, the function of YAP is not known in prostate adenocarcinoma. The purpose of this study was to investigate the role of YAP in tumorigenesis, differentiation of the carcinoma, and prognosis of prostate adenocarcinoma...
June 9, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28593479/rna-binding-protein-dnd1-inhibits-epithelial-mesenchymal-transition-and-cancer-stem-cell-related-traits-on-hepatocellular-carcinoma-cells
#7
Weiling Xu, Fangchao Gong, Ting Zhang, Baorong Chi, Jingyu Wang
OBJECTIVES: To investigate the roles of Dead end 1 (Dnd1) in modulating cancer stem cell-related traits of hepatocellular carcinoma (HCC). RESULTS: Dead end (Dnd1) inhibited spheroid formation, suppressed the expression of stemness-related genes, and increased sensitivity to sorafenib in HCC cells. Mechanistically, Dnd1 could bind to 3'-UTR of LATS2, the key kinase of Hippo pathway, thus elevating LATS2 mRNA stability and its expression, subsequently leading to phosphorylation of YAP and its cytoplasmic retention...
June 7, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/28589555/common-and-distinctive-functions-of-the-hippo-effectors-taz-and-yap-in-skeletal-muscle-stem-cell-function
#8
Congshan Sun, Vanessa De Mello, Abdalla Mohamed, Huascar P Ortuste Quiroga, Amaya Garcia-Munoz, Abdullah Al Bloshi, Annie M Tremblay, Alexander von Kriegsheim, Elaina Collie-Duguid, Neil Vargesson, David Matallanas, Henning Wackerhage, Peter S Zammit
Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analysed Taz in vivo and ex vivo in comparison to Yap. siRNA knockdown or retroviral-mediated expression of wildtype human or constitutively active TAZ mutants in satellite cells showed that TAZ promoted proliferation, a function shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic differentiation of myoblasts, whereas YAP inhibits such differentiation...
June 7, 2017: Stem Cells
https://www.readbyqxmd.com/read/28581498/dystrophin-glycoprotein-complex-sequesters-yap-to-inhibit-cardiomyocyte-proliferation
#9
Yuka Morikawa, Todd Heallen, John Leach, Yang Xiao, James F Martin
The regenerative capacity of the adult mammalian heart is limited because of the reduced ability of cardiomyocytes (CMs) to progress through mitosis(1). The regenerative capacity of endogenous CMs exists at birth but is lost postnatally, with subsequent organ growth occurring through CM hypertrophy(2,3). The Hippo pathway, a conserved kinase cascade, inhibits CM proliferation in the developing heart to control heart size and in the adult heart to prevent regeneration(4,5). The dystrophin glycoprotein complex (DGC), a multicomponent transmembrane complex linking the actin cytoskeleton to extracellular matrix, is essential for CM homeostasis...
June 5, 2017: Nature
https://www.readbyqxmd.com/read/28581486/the-hippo-signaling-functions-through-the-notch-signaling-to-regulate-intrahepatic-bile-duct-development-in-mammals
#10
Nan Wu, Quy Nguyen, Ying Wan, Tiaohao Zhou, Julie Venter, Gabriel A Frampton, Sharon DeMorrow, Duojia Pan, Fanyin Meng, Shannon Glaser, Gianfranco Alpini, Haibo Bai
The Hippo signaling pathway and the Notch signaling pathway are evolutionary conserved signaling cascades that have important roles in embryonic development of many organs. In murine liver, disruption of either pathway impairs intrahepatic bile duct development. Recent studies suggested that the Notch signaling receptor Notch2 is a direct transcriptional target of the Hippo signaling pathway effector YAP, and the Notch signaling is a major mediator of the Hippo signaling in maintaining biliary cell characteristics in adult mice...
June 5, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28579171/the-ndr-lats-protein-kinases-in-immunology-and-cancer-biology
#11
REVIEW
Ahmad A D Sharif, Alexander Hergovich
The NDR (nuclear Dbf2-related)/LATS (large tumour suppressor) family of kinases represents a subclass of the AGC (protein kinase A (PKA)/PKG/PKC-like) group of serine/threonine protein kinases. Members of the NDR/LATS family are vital components of conserved pathways controlling essential cellular processes, such as proliferation (cell cycle progression) and cell death. In particular, the central involvement of NDR/LATS as YAP/TAZ kinases in the Hippo tissue growth control pathway has gained much interest. In this review, we summarize the roles of mammalian NDR1/2 (aka STK38/STK38L) and LATS1/2 in immunity and cancer biology...
June 1, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28570566/targeting-yap-taz-tead-protein-protein-interactions-using-fragment-based-and-computational-modeling-approaches
#12
Hung Yi Kristal Kaan, Adelene Y L Sim, Siew Kim Joyce Tan, Chandra Verma, Haiwei Song
The Hippo signaling pathway, which is implicated in the regulation of organ size, has emerged as a potential target for the development of cancer therapeutics. YAP, TAZ (transcription co-activators) and TEAD (transcription factor) are the downstream transcriptional machinery and effectors of the pathway. Formation of the YAP/TAZ-TEAD complex leads to transcription of growth-promoting genes. Conversely, disrupting the interactions of the complex decreases cell proliferation. Herein, we screened a 1000-member fragment library using Thermal Shift Assay and identified a hit fragment...
2017: PloS One
https://www.readbyqxmd.com/read/28552397/morin-attenuates-diethylnitrosamine-induced-rat-liver-fibrosis-and-hepatic-stellate-cell-activation-by-co-ordinated-regulation-of-hippo-yap-and-tgf-%C3%AE-1-smad-signaling
#13
Perumal NaveenKumar, Perumal MadanKumar, Halagowder Devaraj, Sivasithamparam NiranjaliDevaraj
Despite great progress in understanding the activation of hepatic stellate cells (HSCs) during liver fibrosis, therapeutic approaches to inhibit HSC activation remain very limited. Recent reports highlight Yes-associated protein (Yap) and transforming growth factor-β1 (TGF-β1) as critical regulators of HSC activation and henceforth a compound targeting Hippo/Yap and TGF-β1/Smad pathways would be a potential anti-fibrotic candidate. Morin, a dietary flavonoid, was earlier reported to inhibit HSC proliferation and induction of apoptosis of cultured HSCs, mainly by suppressing Wnt/β-catenin and NF-κB signaling, but its effect on Hippo/Yap and TGF-β1/Smad pathways was not determined...
May 25, 2017: Biochimie
https://www.readbyqxmd.com/read/28550050/loss-of-hippo-signaling-promotes-polyploidy-and-tumorigenesis
#14
(no author information available yet)
YAP activates AKT signaling to promote mitotic arrest, polyploidy, and hepatocellular carcinoma.
May 26, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28543074/wwc3-regulates-the-wnt-and-hippo-pathways-via-dvls-and-lats1-to-suppress-lung-cancer-invasion-and-metastasis
#15
Qiang Han, Xuyong Lin, Xiupeng Zhang, Guiyang Jiang, Yong Zhang, Yuan Miao, Xuezhu Rong, Xiaoying Zheng, Yong Han, Xu Han, Jingjing Wu, Joachim Kremerskothen, Enhua Wang
The scaffolding protein WWC (WW and C2-domain containing) family is known to regulate cell proliferation and organ size via the Hippo signalling pathway. However, the expression level of WWC3 in human tumours and the mechanisms underlying its role in cellular signal transduction have not yet been reported. Herein, we explored the potential roles of WWC3 in lung cancer cells and the corresponding molecular mechanisms. We found low WWC3 expression in both lung cancer cell lines and lung cancer specimens, which was associated with low differentiation, advanced p-TNM stage, positive lymph node metastasis, and poor prognosis in patients with lung cancer...
May 25, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28538170/yap-regulates-actin-dynamics-through-arhgap29-and-promotes-metastasis
#16
Yiting Qiao, Jianxiang Chen, Ying Bena Lim, Megan Louise Finch-Edmondson, Veerabrahma Pratap Seshachalam, Lei Qin, Tingting Jiang, Boon Chuan Low, Himanshu Singh, Chwee Teck Lim, Marius Sudol
Yes-associated protein (YAP) is regulated by mechanical cues via the interaction of the Hippo pathway with cytoskeleton. Previous studies showed that YAP plays a role in regulating the actomyosin network by suppressing Rho GTPase in medaka fish. Here, we identify Rho GTPase activating protein 29 (ARHGAP29) as a transcriptional target of YAP in a human gastric cancer cell line. YAP promotes the expression of ARHGAP29 to suppress the RhoA-LIMK-cofilin pathway, destabilizing F-actin. The overexpression of YAP causes cytoskeletal rearrangement by altering the dynamics of F-actin/G-actin turnover, thus promoting migration...
May 23, 2017: Cell Reports
https://www.readbyqxmd.com/read/28528906/warts-signaling-controls-organ-and-body-growth-through-regulation-of-ecdysone
#17
Morten E Moeller, Stanislav Nagy, Stephan U Gerlach, Karen C Soegaard, E Thomas Danielsen, Michael J Texada, Kim F Rewitz
Coordination of growth between individual organs and the whole body is essential during development to produce adults with appropriate size and proportions [1, 2]. How local organ-intrinsic signals and nutrient-dependent systemic factors are integrated to generate correctly proportioned organisms under different environmental conditions is poorly understood. In Drosophila, Hippo/Warts signaling functions intrinsically to regulate tissue growth and organ size [3, 4], whereas systemic growth is controlled via antagonistic interactions of the steroid hormone ecdysone and nutrient-dependent insulin/insulin-like growth factor (IGF) (insulin) signaling [2, 5]...
June 5, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28524356/association-between-yap-expression-in-neoplastic-and-non-neoplastic-breast-tissue-with-arsenic-urinary-levels
#18
Gladis Michel-Ramirez, Rogelio Recio-Vega, Guadalupe Ocampo-Gomez, Eduardo Palacios-Sanchez, Manuel Delgado-Macias, Manuel Delgado-Gaona, Robert Clark Lantz, Jay Gandolfi, Tania Gonzalez-Cortes
The Hippo pathway regulates cell proliferation and apoptosis and it has been noted that loss of critical components of this pathway can lead to uncontrolled cell growth. Yes-associated protein (YAP) is an important component of this Hippo pathway because YAP is the nuclear effector of the Hippo tumor suppressor pathway and it is crucial for the response to oxidative stress induced by cellular process and by different xenobiotics, including arsenic. It has been proposed that YAP dysregulation can contribute to a malignant cellular phenotype acting as both a tumor suppressor and an oncogene...
May 19, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28515457/crystal-structure-of-taz-tead-complex-reveals-a-distinct-interaction-mode-from-that-of-yap-tead-complex
#19
Hung Yi Kristal Kaan, Siew Wee Chan, Siew Kim Joyce Tan, Fusheng Guo, Chun Jye Lim, Wanjin Hong, Haiwei Song
The Hippo pathway is a tumor suppressor pathway that is implicated in the regulation of organ size. The pathway has three components: the upstream regulatory factors, the kinase core, and the downstream transcriptional machinery, which consists of YAP, TAZ (transcription co-activators) and TEAD (transcription factor). Formation of YAP/TAZ-TEAD complexes leads to the transcription of growth-promoting genes. Herein, we report the crystal structure of TAZ-TEAD4 complex, which reveals two binding modes. The first is similar to the published YAP-TEAD structure...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28504269/yap-regulates-cell-mechanics-by-controlling-focal-adhesion-assembly
#20
Giorgia Nardone, Jorge Oliver-De La Cruz, Jan Vrbsky, Cecilia Martini, Jan Pribyl, Petr Skládal, Martin Pešl, Guido Caluori, Stefania Pagliari, Fabiana Martino, Zuzana Maceckova, Marian Hajduch, Andres Sanz-Garcia, Nicola Maria Pugno, Gorazd Bernard Stokin, Giancarlo Forte
Hippo effectors YAP/TAZ act as on-off mechanosensing switches by sensing modifications in extracellular matrix (ECM) composition and mechanics. The regulation of their activity has been described by a hierarchical model in which elements of Hippo pathway are under the control of focal adhesions (FAs). Here we unveil the molecular mechanism by which cell spreading and RhoA GTPase activity control FA formation through YAP to stabilize the anchorage of the actin cytoskeleton to the cell membrane. This mechanism requires YAP co-transcriptional function and involves the activation of genes encoding for integrins and FA docking proteins...
May 15, 2017: Nature Communications
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