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Hippo signalling

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https://www.readbyqxmd.com/read/28315837/a-search-for-genes-mediating-the-growth-promoting-function-of-tgf%C3%AE-in-the-drosophila-melanogaster-wing-disc
#1
Covadonga F Hevia, Ana López-Varea, Nuria Esteban, Jose F de Celis
TGFβ signalling has a complex influence in cell proliferation, acting to stop cell division in differentiating cells, but also promoting cell division in immature cells. The activity of the pathway in Drosophila is mostly required to stimulate the proliferation of neural and epithelial tissues. Most interestingly, this function is not absolutely required for cell division, but it is needed for these tissues to reach their correct size. It is not known how TGFβ signalling promotes cell division in imaginal discs, or what are the interactions between TGFβ activity and other signalling pathways regulating cell proliferation...
March 17, 2017: Genetics
https://www.readbyqxmd.com/read/28315521/systematic-morphological-profiling-of-human-gene-and-allele-function-via-cell-painting
#2
Mohammad Hossein Rohban, Shantanu Singh, Xiaoyun Wu, Julia B Berthet, Mark-Anthony Bray, Yashaswi Shrestha, Xaralabos Varelas, Jesse S Boehm, Anne E Carpenter
We hypothesized that human genes and disease-associated alleles might be systematically functionally annotated using morphological profiling of cDNA constructs, via a microscopy-based Cell Painting assay. Indeed, 50% of the 220 tested genes yielded detectable morphological profiles, which grouped into biologically meaningful gene clusters consistent with known functional annotation (e.g., the RAS-RAF-MEK-ERK cascade). We used novel subpopulation-based visualization methods to interpret the morphological changes for specific clusters...
March 18, 2017: ELife
https://www.readbyqxmd.com/read/28299672/roles-of-runx-in-hippo-pathway-signaling
#3
Antonino Passaniti, Jessica L Brusgard, Yiting Qiao, Marius Sudol, Megan Finch-Edmondson
The Runt-domain (RD) transcription factors (RUNX genes) are an important family of transcriptional mediators that interact with a variety of proteins including the Hippo pathway effector proteins, YAP and TAZ. In this chapter we focus on two examples of RUNX-TAZ/YAP interactions that have particular significance in human cancer. Specifically, recent evidence has found that RUNX2 cooperates with TAZ to promote epithelial to mesenchymal transition mediated by the soluble N-terminal ectodomain of E-Cadherin, sE-Cad...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28293931/investigation-of-the-possible-role-of-the-hippo-yap1-pathway-in-asthma-and-allergy
#4
Lili E Fodor, András Gézsi, Ldikó Ungvári, Agnes F Semsei, Zsófia Gál, Adrienne Nagy, Gabriella Gálffy, Lilla Tamási, András Kiss, Péter Antal, Csaba Szalai
PURPOSE: Several lines of evidence indicate that the Hippo/Yes-associated protein 1 (YAP1) pathways might play a role in the pathogenesis of asthma. To investigate the possible role of the Hippo/YAP1 pathway in the pathogenesis of asthma or its phenotypes. METHODS: The levels of gene expressions of the members of the Hippo/YAP1 were compared. The presence of the proteins of the YAP1 and FRMD6 were analyzed with Western blot in induced sputum of 18 asthmatic subjects and 10 control subjects...
May 2017: Allergy, Asthma & Immunology Research
https://www.readbyqxmd.com/read/28292426/kibra-and-merlin-activate-the-hippo-pathway-spatially-distinct-from-and-independent-of-expanded
#5
Ting Su, Michael Z Ludwig, Jiajie Xu, Richard G Fehon
The Hippo pathway is emerging as a key evolutionarily conserved signaling mechanism that controls organ size. Three membrane-associated proteins, Kibra, Merlin, and Expanded, regulate pathway activity, but the precise molecular mechanism by which they function is still poorly understood. Here we provide evidence that Merlin and Kibra activate Hippo signaling in parallel to Expanded at a spatially distinct cellular domain, the medial apical cortex. Merlin and Kibra together recruit the adapter protein Salvador, which in turn recruits the core kinase Hippo...
March 13, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28281933/spatial-regulation-of-araf-controls-the-mst2-hippo-pathway
#6
Jens Rauch, Walter Kolch
The RAF-MAPK signaling pathway regulates several very diverse cellular processes such as proliferation, differentiation, apoptosis, and transformation. While the canonical function of RAF kinases within the MAPK pathway is the activation of MEK, our group could demonstrate an important crosstalk between RAF signaling and the pro-apoptotic mammalian sterile 20-like kinase (MST2) tumor suppressor pathway in several cancer entities, including head and neck, colon, and breast. Here, the RAF kinases CRAF and ARAF sequester and inhibit the pro-apoptotic kinase MST2 independently of their own kinase activity...
March 10, 2017: Small GTPases
https://www.readbyqxmd.com/read/28280861/a-growing-role-for-the-hippo-signaling-pathway-in-the-heart
#7
REVIEW
Yu Zhang, Dominic P Del Re
Heart disease is a major cause of clinical morbidity and mortality, and a significant health and economic burden worldwide. The loss of functional cardiomyocytes, often a result of myocardial infarction, leads to impaired cardiac output and ultimately heart failure. Therefore, efforts to improve cardiomyocyte viability and stimulate cardiomyocyte proliferation remain attractive therapeutic goals. Originally identified in Drosophila, the Hippo signaling pathway is highly conserved from flies to humans and regulates organ size through modulation of both cell survival and proliferation...
March 10, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28279717/yap-and-wwtr1-new-targets-for-skin-cancer-treatment
#8
Thomas Andl, Linli Zhou, Kun Yang, Ana Luisa Kadekaro, Yuhang Zhang
The core components of the Hippo signaling pathway are a cascade of kinases that govern the phosphorylation of downstream transcriptional co-activators, namely, YES-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ). The Hippo signaling pathway is considered an important tumor-suppressor pathway, and its dysregulation has been noted in a variety of human cancers, in which YAP/WWTR1 enable cancerous cells to overcome contact inhibition, and to grow and spread uncontrollably...
March 6, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28274274/a-novel-form-of-necrosis-triad-occurs-in-human-huntington-s-disease
#9
Emiko Yamanishi, Kazuko Hasegawa, Kyota Fujita, Shizuko Ichinose, Saburo Yagishita, Miho Murata, Kazuhiko Tagawa, Takumi Akashi, Yoshinobu Eishi, Hitoshi Okazawa
We previously reported transcriptional repression-induced atypical cell death of neuron (TRIAD), a new type of necrosis that is mainly regulated by Hippo pathway signaling and distinct from necroptosis regulated by RIP1/3 pathway. Here, we examined the ultrastructural and biochemical features of neuronal cell death in the brains of human HD patients in parallel with the similar analyses using mutant Htt-knock-in (Htt-KI) mice. LATS1 kinase, the critical regulator and marker of TRIAD, is actually activated in cortical neurons of postmortem human HD and of Htt-KI mouse brains, while apoptosis promoter kinase Plk1 was inactivated in human HD brains...
March 8, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28273460/agrin-as-a-mechanotransduction-signal-regulating-yap-through-the-hippo-pathway
#10
Sayan Chakraborty, Kizito Njah, Ajaybabu V Pobbati, Ying Bena Lim, Anandhkumar Raju, Manikandan Lakshmanan, Vinay Tergaonkar, Chwee Teck Lim, Wanjin Hong
The Hippo pathway effectors YAP and TAZ act as nuclear sensors of mechanical signals in response to extracellular matrix (ECM) cues. However, the identity and nature of regulators in the ECM and the precise pathways relaying mechanoresponsive signals into intracellular sensors remain unclear. Here, we uncover a functional link between the ECM proteoglycan Agrin and the transcriptional co-activator YAP. Importantly, Agrin transduces matrix and cellular rigidity signals that enhance stability and mechanoactivity of YAP through the integrin-focal adhesion- and Lrp4/MuSK receptor-mediated signaling pathways...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28265104/mir-285-yki-mask-double-negative-feedback-loop-mediates-blood-brain-barrier-integrity-in-drosophila
#11
Dong Li, Yanling Liu, Chunli Pei, Peng Zhang, Linqing Pan, Jing Xiao, Songshu Meng, Zengqiang Yuan, Xiaolin Bi
The Hippo signaling pathway is highly conserved from Drosophila to mammals and plays a central role in maintaining organ size and tissue homeostasis. The blood-brain barrier (BBB) physiologically isolates the brain from circulating blood or the hemolymph system, and its integrity is strictly maintained to perform sophisticated neuronal functions. Until now, the underlying mechanisms of subperineurial glia (SPG) growth and BBB maintenance during development are not clear. Here, we report an miR-285-Yorkie (Yki)/Multiple Ankyrin repeats Single KH domain (Mask) double-negative feedback loop that regulates SPG growth and BBB integrity...
March 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28260491/control-of-myofibroblast-differentiation-and-function-by-cytoskeletal-signaling
#12
REVIEW
N Sandbo, L V Smolyaninova, S N Orlov, N O Dulin
The cytoskeleton consists of three distinct types of protein polymer structures - microfilaments, intermediate filaments, and microtubules; each serves distinct roles in controlling cell shape, division, contraction, migration, and other processes. In addition to mechanical functions, the cytoskeleton accepts signals from outside the cell and triggers additional signals to extracellular matrix, thus playing a key role in signal transduction from extracellular stimuli through dynamic recruitment of diverse intermediates of the intracellular signaling machinery...
December 2016: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28257933/genetic-ablation-of-the-mammalian-sterile-20-like-kinase-1-mst1-improves-cell-reprogramming-efficiency-and-increases-induced-pluripotent-stem-cell-proliferation-and-survival
#13
Abigail Robertson, Tamer M A Mohamed, Zeinab El Maadawi, Nicholas Stafford, Thuy Bui, Dae-Sik Lim, Elizabeth J Cartwright, Delvac Oceandy
Adult fibroblasts can be reprogrammed into induced pluripotent stem cells (iPSC) for use in various applications. However, there are challenges in iPSC generation including low reprogramming efficiency, yield, cell survival and viability. Since the Hippo signalling pathway is a key pathway involved in regulating cell proliferation and survival, we here test whether modification of the Hippo pathway will enhance the efficiency of iPSC generation and improve their survival. The Hippo pathway was modified by genetic ablation of the mammalian sterile-20 like kinase 1 (Mst1), a major component of the pathway...
February 27, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28250241/stimulation-of-ovarian-follicle-growth-following-ampk-inhibition
#14
Xiaowei Lu, Song Guo, Yuan Cheng, Jae-Hong Kim, Yi Feng, Yun Feng
Previous studies showed that the protein kinase B (Akt)-mammalian target of rapamycin (mTOR) and Hippo signaling-Yes associated protein (YAP) pathways play important roles in promoting follicle growth. Additionally, other studies demonstrated that 5' adenosine monophosphate-activated protein kinase (AMPK) is an upstream regulatory element of mTOR and YAP. Here, we used AMPK inhibitor (Compound C) to in vitro culture ovaries from 10-day-old mice followed by in vivo grafting into adult hosts, or to in situ treat ovaries of 3-week-old mice by intrabursal injection followed by gonadotropin stimulation...
March 1, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28249901/endothelin-promotes-colorectal-tumorigenesis-by-activating-yap-taz
#15
Zhen Wang, Peng Liu, Xin Zhou, Tianxiang Wang, Xu Feng, Yi-Ping Sun, Yue Xiong, Hai-Xin Yuan, Kun-Liang Guan
Endothelin receptor A (ETAR) promotes tumorigenesis by stimulating cell proliferation, migration and survival. However, the mechanism of ETAR in promoting tumor growth is largely unknown. In this study, we demonstrate that ETAR stimulates colon cell proliferation, migration, and tumorigenesis through the activation of YAP/TAZ, two transcription co-activators of the Hippo tumor suppressor pathway. Endothelin-1 (ET-1) treatment induced YAP/TAZ dephosphorylation, nuclear accumulation, and transcriptional activation in multiple colon cancer cells...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28249813/induction-of-chromosome-instability-by-activation-of-yes-associated-protein-and-forkhead-box-m1-in-liver-cancer
#16
Sofia M E Weiler, Federico Pinna, Thomas Wolf, Teresa Lutz, Aman Geldiyev, Carsten Sticht, Maria Knaub, Stefan Thomann, Michaela Bissinger, Shan Wan, Stephanie Rössler, Diana Becker, Norbert Gretz, Hauke Lang, Frank Bergmann, Vladimir Ustiyan, Tatiana V Kalin, Stephan Singer, Ju-Seog Lee, Jens U Marquardt, Peter Schirmacher, Vladimir V Kalinichenko, Kai Breuhahn
BACKGROUND & AIMS: Many different types of cancer cells have chromosome instability. The hippo pathway leads to phosphorylation of the transcriptional activator yes associated protein 1 (YAP1, YAP), which regulates proliferation and has been associated with development of liver cancer. We investigated the effects of hippo signaling via YAP on chromosome stability and hepatocarcinogenesis in humans and mice. METHODS: We analyzed transcriptome data from 242 patients with hepatocellular carcinoma (HCC) to search for gene signatures associated with chromosomal instability; we investigated associations with overall survival time and cancer recurrence using Kaplan-Meier curves...
February 26, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28246211/apoptosis-restores-cellular-density-by-eliminating-a-physiologically-or-genetically-induced-excess-of-enterocytes-in-the-drosophila-midgut
#17
Rihab Loudhaief, Alexandra Brun-Barale, Olivia Benguettat, Marie-Paule Nawrot-Esposito, David Pauron, Marcel Amichot, Armel Gallet
Using pathogens or high levels of opportunistic bacteria to damage the gut, studies in Drosophila have identified many signaling pathways involved in gut regeneration. Dying cells emit signaling molecules that accelerate intestinal stem cell proliferation and progenitor differentiation to replace the dying cells quickly. This process has been named 'regenerative cell death'. Here, mimicking environmental conditions, we show that the ingestion of low levels of opportunistic bacteria was sufficient to launch an accelerated cellular renewal program despite the brief passage of bacteria in the gut and the absence of cell death and this is is due to the moderate induction of the JNK pathway that stimulates stem cell proliferation...
March 1, 2017: Development
https://www.readbyqxmd.com/read/28245464/the-hippo-signaling-pathway-regulates-ovarian-function-via-the-proliferation-of-ovarian-germline-stem-cells
#18
Haifeng Ye, Xiaoyan Li, Tuochen Zheng, Chuan Hu, Zezheng Pan, Jian Huang, Jia Li, Wei Li, Yuehui Zheng
OBJECTIVE: To improve the separation, identification and cultivation of ovarian germline stem cells (OGSCs), to clarify the relationship between the Hippo signaling pathway effector YAP1 and the proliferation and differentiation of OGSCs in vitro and to identify the major contribution of Hippo signaling to ovarian function. METHODS: Two-step enzymatic separation processes and magnetic separation were used to isolate and identify OGSCs by determining the expression of Mvh, Oct4, Nanog, Fragilis and Stella markers...
February 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28244491/new-evidence-for-non-canonical-hippo-signaling-in-cancer
#19
Jonathan Cooper, Filippo G Giancotti
The molecular mechanisms governing self-renewal and differentiation of the mammary epithelium are incompletely defined; a better understanding of the events implicated in the specification and expansion of luminal progenitors is of particular importance as many breast cancers originate from their transformation. Britschgi et al. found that, in addition to phosphorylating and inactivating YAP, LATS functions as a scaffold to facilitate estrogen receptor-α ubiquitylation by the E3 ligase CRL4 and consequently suppresses luminal progenitor specification and expansion...
February 28, 2017: Cell Research
https://www.readbyqxmd.com/read/28239148/amotl1-mediates-sequestration-of-the-hippo-effector-yap1-downstream-of-fat4-to-restrict-heart-growth
#20
Chiara V Ragni, Nicolas Diguet, Jean-François Le Garrec, Marta Novotova, Tatiana P Resende, Sorin Pop, Nicolas Charon, Laurent Guillemot, Lisa Kitasato, Caroline Badouel, Alexandre Dufour, Jean-Christophe Olivo-Marin, Alain Trouvé, Helen McNeill, Sigolène M Meilhac
Although in flies the atypical cadherin Fat is an upstream regulator of Hippo signalling, the closest mammalian homologue, Fat4, has been shown to regulate tissue polarity rather than growth. Here we show in the mouse heart that Fat4 modulates Hippo signalling to restrict growth. Fat4 mutant myocardium is thicker, with increased cardiomyocyte size and proliferation, and this is mediated by an upregulation of the transcriptional activity of Yap1, an effector of the Hippo pathway. Fat4 is not required for the canonical activation of Hippo kinases but it sequesters a partner of Yap1, Amotl1, out of the nucleus...
February 27, 2017: Nature Communications
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