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Hippo signalling

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https://www.readbyqxmd.com/read/27900010/a-novel-mutation-of-the-fat2-gene-in-spinal-meningioma
#1
Genshu Tate, Koji Kishimoto, Toshiyuki Mitsuya
Meningiomas may be classified as neurofibromin 2 (NF2)-associated and non-NF2 meningiomas depending on the presence or absence of molecular alterations in the NF2 gene. One of the characteristic histological features of meningiomas is the whorl formation of neoplastic arachnoid cells. NF2 is a human homolog of the Drosophila gene, Merlin (Mer). In humans, NF2 is the gene responsible for the disease neurofibromatosis type II, which results in the development of brain tumors, including acoustic neurinoma and meningioma...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27885187/-role-of-hippo-yap-taz-signaling-pathway-in-mechanotransduction
#2
Erika Ishihara, Hiroshi Nishina
Transcriptional coactivators YAP(yes associated protein)and TAZ(transcriptional coactivator with PDZ-binding motif)regulate gene expression through binding to transcription factors. Recently, some studies showed that YAP/TAZ activity responded to mechanical inputs such as stiffness of the extracellular matrix and the mechanical regulation of YAP/TAZ controlled cell proliferation or differentiation. Additionally, we revealed important roles of YAP in tissue formation and homeostasis through cellular tension and pressure...
2016: Clinical Calcium
https://www.readbyqxmd.com/read/27883091/mycobacterium-tuberculosis-triggered-hippo-pathway-orchestrates-cxcl1-2-expression-to-modulate-host-immune-responses
#3
Monoranjan Boro, Vikas Singh, Kithiganahalli Narayanaswamy Balaji
Mycobacterium tuberculosis (Mtb) pathogenesis encompasses a plethora of finely regulated alterations within the host which eventually coin the outcome of infection. Chemokines are important components in directing immune cell recruitment to the site of infection, and shaping the disease progression. Here, we demonstrate that Hippo (mammalian sterile 20-like 1 and 2 kinases, MST1/2, in mammals), is activated during mycobacterial infection in a toll-like receptor (TLR) 2-interleukin receptor-1 associated kinases (IRAK1/4)-dependent manner...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881410/taz-activation-drives-fibroblast-spheroid-growth-expression-of-pro-fibrotic-paracrine-signals-and-context-dependent-ecm-gene-expression
#4
Amy J Jorgenson, Kyoung Moo Choi, Delphine Sicard, Karry M J Smith, Samantha E Hiemer, Xaralabos Varelas, Daniel J Tschumperlin
Recent studies have implicated the Hippo pathway and its transcriptional effectors YAP and TAZ as necessary for fibroblast activation and tissue fibrosis. To test the specific and sufficient roles for TAZ in driving autonomous fibroblast activation, we cultured NIH3T3 fibroblasts expressing a doxycycline-inducible nuclear-localized mutant of TAZ (TAZ4SA) in scaffold-free 3D hanging drop spheroids, or on matrices of specified mechanical rigidity. Control NIH3T3 fibroblasts formed spheroids in hanging drop culture that remained stable and neither increased nor decreased in size significantly over 15 days...
November 23, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27881216/interacting-network-of-hippo-wnt-%C3%AE-catenin-and-notch-signaling-represses-liver-tumor-formation
#5
Wantae Kim, Sanjoy Kumar Khan, Yingzi Yang
Acquiring a selective growth advantage by breaking the proliferation barrier established by gatekeeper genes is a centrally important event in tumor formation. Removal of mammalian Hippo kinase Mst1 and Mst2 in hepatocytes leads to very rapid hepatocellular carcinoma (HCC) formation, indicating that the Hippo signaling pathway is a critical gatekeeper in hepatocytes that restrains abnormal growth. By rigorous genetic approaches, we have identified an interacting network of the Hippo, Wnt/β-catenin and Notch signaling pathways that controls organ size and HCC development...
November 24, 2016: BMB Reports
https://www.readbyqxmd.com/read/27877230/transcriptional-cofactor-mask2-is-required-for-yap-induced-cell-growth-and-migration-in-bladder-cancer-cell
#6
Liang Dong, Fan Lin, Wanjun Wu, Weiren Huang, Zhiming Cai
The highly conserved Hippo signaling pathway is an important pathway involved in tumorigenesis and development. In previous studies, YAP, the transcription coactivator of Hippo pathway, is found to be highly expressed in many clinical bladder cancer samples. To investigate the function of YAP and its cofactor Mask2 in bladder cancer, we overexpress YAP in bladder cancer cells and discover that YAP is able to promote bladder cancer cell growth and migration. In addition, we provide evidence that knockdown of Mask2 is able to repress bladder cancer cell growth and migration...
2016: Journal of Cancer
https://www.readbyqxmd.com/read/27875740/conditional-knockout-of-tfpi-1-in-vsmcs-of-mice-accelerates-atherosclerosis-by-enhancing-amot-yap-pathway
#7
Jiajun Xiao, Kaiyue Jin, Jiping Wang, Jing Ma, Jin Zhang, Nan Jiang, Huijun Wang, Xinping Luo, Jian Fei, Zhugang Wang, Xiao Yang, Duan Ma
BACKGROUND: Tissue factor pathway inhibitor-1 (TFPI-1) has multiple functions and its precise role and molecular mechanism during the development of atherosclerosis are not clear. OBJECTIVES: To determine the effect and molecular mechanism of TFPI-1 deficiency in vascular smooth muscle cells (VSMCs) in atherosclerosis in the apolipoprotein E knockout (ApoE(-/-)) mouse. METHODS AND RESULTS: A mouse model with a conditional knockout of TFPI-1 in VSMCs in an atherosclerosis-prone background (ApoE(-/-)) was generated...
November 12, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27874005/the-hippo-signalling-pathway-coordinates-organ-growth-and-limits-developmental-variability-by-controlling-dilp8-expression
#8
Emilie Boone, Julien Colombani, Ditte S Andersen, Pierre Léopold
Coordination of organ growth during development is required to generate fit individuals with fixed proportions. We recently identified Drosophila Dilp8 as a key hormone in coupling organ growth with animal maturation. In addition, dilp8 mutant flies exhibit elevated fluctuating asymmetry (FA) demonstrating a function for Dilp8 in ensuring developmental stability. The signals regulating Dilp8 activity during normal development are not yet known. Here, we show that the transcriptional co-activators of the Hippo (Hpo) pathway, Yorkie (Yki, YAP/TAZ) and its DNA-binding partner Scalloped (Sd), directly regulate dilp8 expression through a Hpo-responsive element (HRE) in the dilp8 promoter...
November 22, 2016: Nature Communications
https://www.readbyqxmd.com/read/27869648/hippo-signaling-interactions-with-wnt-%C3%AE-catenin-and-notch-signaling-repress-liver-tumorigenesis
#9
Wantae Kim, Sanjoy Kumar Khan, Jelena Gvozdenovic-Jeremic, Youngeun Kim, Jason Dahlman, Hanjun Kim, Ogyi Park, Tohru Ishitani, Eek-Hoon Jho, Bin Gao, Yingzi Yang
Malignant tumors develop through multiple steps of initiation and progression, and tumor initiation is of singular importance in tumor prevention, diagnosis, and treatment. However, the molecular mechanism whereby a signaling network of interacting pathways restrains proliferation in normal cells and prevents tumor initiation is still poorly understood. Here, we have reported that the Hippo, Wnt/β-catenin, and Notch pathways form an interacting network to maintain liver size and suppress hepatocellular carcinoma (HCC)...
November 21, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27864128/prostaglandin-e2-activates-yap-and-a-positive-signaling-loop-to-promote-colon-regeneration-following-colitis-but-also-carcinogenesis-in-mice
#10
Han-Byul Kim, Minchul Kim, Young-Soo Park, Intae Park, Tackhoon Kim, Sung-Yeun Yang, Charles J Cho, DaeHee Hwang, Jin-Hak Jung, Sanford D Markowitz, Sung Wook Hwang, Suk-Kyun Yang, Dae-Sik Lim, Seung-Jae Myung
BACKGROUND & AIMS: Prostaglandin E2 (PGE2) is mediator of inflammation that regulates tissue regeneration, but its continual activation has been associated with carcinogenesis. Little is known about factors in the PGE2 signaling pathway that contribute to tumor formation. We investigated whether yes associated protein 1 (YAP1), a transcriptional co-activator in the Hippo signaling pathway, mediates PGE2 function. METHODS: DLD-1 and SW480 colon cancer cell lines were transfected with vectors expressing transgenes or small hairpin RNAs and incubated with recombinant PGE2, with or without pharmacologic inhibitors of signaling proteins, and analyzed by immunoblot, immunofluorescence, quantitative reverse transcription PCR, transcriptional reporter, and proliferation assays...
November 15, 2016: Gastroenterology
https://www.readbyqxmd.com/read/27855662/microarray-expression-profile-analysis-of-mrnas-and-long-non-coding-rnas-in-pulmonary-tuberculosis-with-different-traditional-chinese-medicine-syndromes
#11
Ting-Ting Jiang, Li-Liang Wei, Li-Ying Shi, Zhong-Liang Chen, Chong Wang, Chang-Ming Liu, Zhong-Jie Li, Ji-Cheng Li
BACKGROUND: Combination chemotherapy with Western anti-tuberculosis (TB) drugs is the mainstay of TB treatment. Chinese herbal medicines with either heat clearing and detoxifying effects or nourishing Yin and reducing fire effects have been used to treat TB based on the Traditional Chinese Medicine (TCM) syndromes of TB patients. This study analyzed the expression profiles of long non-coding RNAs (lncRNAs) and mRNAs in TB patients with different TCM syndromes. METHODS: TB patients were classified as pulmonary Yin deficiency (PYD) syndrome, hyperactivity of fire due to Yin deficiency (HFYD) syndrome, and deficiency of Qi and Yin (DQY) syndrome...
November 17, 2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27851961/wip-drives-tumor-progression-through-yap-taz-dependent-autonomous-cell-growth
#12
Ricardo Gargini, Maribel Escoll, Esther García, Ramón García-Escudero, Francisco Wandosell, Inés María Antón
In cancer, the deregulation of growth signaling pathways drives changes in the cell's architecture and its environment that allow autonomous growth of tumors. These cells then acquire a tumor-initiating "stemness" phenotype responsible for disease advancement to more aggressive stages. Here, we show that high levels of the actin cytoskeleton-associated protein WIP (WASP-interacting protein) correlates with tumor growth, both of which are linked to the tumor-initiating cell phenotype. We find that WIP controls tumor growth by boosting signals that stabilize the YAP/TAZ complex via a mechanism mediated by the endocytic/endosomal system...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27847303/sumoylation-of-large-tumor-suppressor-1-at-lys751-attenuates-its-kinase-activity-and-tumor-suppressor-functions
#13
Liu Mei, Lianwen Yuan, Wei Shi, Shihao Fan, Chao Tang, Xueying Fan, Wanlei Yang, Yu Qian, Musaddique Hussain, Ximei Wu
Large tumor suppressor (Lats) plays a critical role in maintaining cellular homeostasis and is the core to mediate Hippo growth-inhibitory signaling pathway. SUMOylation is a reversible and dynamic process that regulates a variety of cell functions. Here, we show that SUMOylation of Lats1 affects its kinase activity specifically towards Hippo signaling. Small ubiquitin-like modifier (SUMO) 1 interacts with and directly SUMOylates Lats1, whereas loss of SUMOylation pathway function disrupts Lats1 SUMOylation...
November 12, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27836834/signaling-cross-talk-between-tgf-%C3%AE-smad-and-other-signaling-pathways
#14
Kunxin Luo
Cytokines of the transforming growth factor β (TGF-β) family, including TGF-βs, bone morphogenic proteins (BMPs), activins, and Nodal, play crucial roles in embryonic development and adult tissue homeostasis by regulating cell proliferation, survival, and differentiation, as well as stem-cell self-renewal and lineage-specific differentiation. Smad proteins are critical downstream mediators of these signaling activities. In addition to regulating the transcription of direct target genes of TGF-β, BMP, activin, or Nodal, Smad proteins also participate in extensive cross talk with other signaling pathways, often in a cell-type- or developmental stage-specific manner...
November 11, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27826870/hippo-signaling-in-mitosis-an-updated-view-in-light-of-the-men-pathway
#15
Alexander Hergovich
The Hippo pathway is an essential tumor suppressor signaling network that coordinates cell proliferation, death, and differentiation in higher eukaryotes. Intriguingly, the core components of the Hippo pathway are conserved from yeast to man, with the yeast analogs of mammalian MST1/2 (fly Hippo), MOB1 (fly Mats), LATS1/2 (fly Warts), and NDR1/2 (fly Tricornered) functioning as essential components of the mitotic exit network (MEN). Here, we update our previous summary of mitotic functions of Hippo core components in Drosophila melanogaster and mammals, with particular emphasis on similarities between the yeast MEN pathway and mitotic Hippo signaling...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27826852/regulation-of-mitotic-exit-in-saccharomyces-cerevisiae
#16
Bàrbara Baro, Ethel Queralt, Fernando Monje-Casas
The Mitotic Exit Network (MEN) is an essential signaling pathway, closely related to the Hippo pathway in mammals, which promotes mitotic exit and initiates cytokinesis in the budding yeast Saccharomyces cerevisiae. Here, we summarize the current knowledge about the MEN components and their regulation.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27818180/rac1-mediated-dna-damage-and-inflammation-promote-nf2-tumorigenesis-but-also-limit-cell-cycle-progression
#17
Yuhao Shi, Saumya R Bollam, Shannon M White, Sean Z Laughlin, Garrett T Graham, Mandheer Wadhwa, Hengye Chen, Chan Nguyen, Jeremie Vitte, Marco Giovannini, Jeffery Toretsky, Chunling Yi
Merlin encoded by the Nf2 gene is a bona fide tumor suppressor that has been implicated in regulation of both the Hippo-Yap and Rac1-Pak1 pathways. Using genetically engineered murine liver models, we show that co-deletion of Rac1 with Nf2 blocks tumor initiation but paradoxically exacerbates hepatomegaly induced by Nf2 loss, which can be suppressed either by treatment with pro-oxidants or by co-deletion of Yap. Our results suggest that while Yap acts as the central driver of proliferation during Nf2 tumorigenesis, Rac1 primarily functions as an inflammation switch by inducing reactive oxygen species that, on one hand, induce nuclear factor κB signaling and expression of inflammatory cytokines, and on the other activate p53 checkpoint and senescence programs dampening the cyclin D1-pRb-E2F1 pathway...
November 21, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27812538/proproliferative-and-antiapoptotic-action-of-exogenously-introduced-yap-in-pancreatic-%C3%AE-cells
#18
Ting Yuan, Sahar Rafizadeh, Zahra Azizi, Blaz Lupse, Kanaka Durga Devi Gorrepati, Sushil Awal, Jose Oberholzer, Kathrin Maedler, Amin Ardestani
Loss of functional pancreatic β cells is a hallmark of both type 1 and 2 diabetes. Identifying the pathways that promote β cell proliferation and/or block β cell apoptosis is a potential strategy for diabetes therapy. The transcriptional coactivator Yes-associated protein (YAP), a major downstream effector of the Hippo signaling pathway, is a key regulator of organ size and tissue homeostasis by modulating cell proliferation and apoptosis. YAP is not expressed in mature primary human and mouse β cells. We aimed to identify whether reexpression of a constitutively active form of YAP promotes β cell proliferation/survival...
November 3, 2016: JCI Insight
https://www.readbyqxmd.com/read/27812180/comparative-gene-expression-profiling-of-primary-and-metastatic-renal-cell-carcinoma-stem-cell-like-cancer-cells
#19
Mohammed I Khan, Anna M Czarnecka, Sławomir Lewicki, Igor Helbrecht, Klaudia Brodaczewska, Irena Koch, Robert Zdanowski, Magdalena Król, Cezary Szczylik
BACKGROUND: Recent advancement in cancer research has shown that tumors are highly heterogeneous, and multiple phenotypically different cell populations are found in a single tumor. Cancer development and tumor growth are driven by specific types of cells-stem cell-like cancer cells (SCLCCs)-which are also responsible for metastatic spread and drug resistance. This research was designed to verify the presence of SCLCCs in renal cell cancer cell lines. Subsequently, we aimed to characterize phenotype and cell biology of CD105+ cells, defined previously as renal cell carcinoma tumor-initiating cells...
2016: PloS One
https://www.readbyqxmd.com/read/27809333/yap-tead-and-hnf4%C3%AE-repress-reciprocally-to-regulate-hepatocarcinogenesis
#20
Wang-Yu Cai, Ling-Yun Lin, Han Hao, Sai-Man Zhang, Fei Ma, Xin-Xin Hong, Hui Zhang, Qing-Feng Liu, Guo-Dong Ye, Guang-Bin Sun, Yun-Jia Liu, Sheng-Nan Li, Yuan-Yuan Xie, Jian-Chun Cai, Li Bo-An
: Great progress has been achieved in the study of Hippo signaling in regulating tumorigenesis; however, the downstream molecular events that mediate this process have not been completely defined. Moreover, the regulation of Hippo signaling during tumorigenesis in hepatocellular carcinoma (HCC) remains largely unknown. In the present study, we systematically investigated the relationship between YAP-TEAD and HNF4α in the hepatocarcinogenesis of HCC cells. Our results indicated that HNF4α expression was negatively regulated by YAP1 in HCC cells via a ubiquitin proteasome pathway...
November 3, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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