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https://www.readbyqxmd.com/read/29457552/reciprocal-regulation-of-yap-taz-by-the-hippo-pathway-and-the-small-gtpase-pathway
#1
Ju-Won Jang, Min-Kyu Kim, Suk-Chul Bae
Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) (YAP/TAZ) are transcriptional coactivators that regulate genes involved in proliferation and transformation by interacting with DNA-binding transcription factors. Remarkably, YAP/TAZ are essential for cancer initiation or growth of most solid tumors. Their activation induces cancer stem cell attributes, proliferation, and metastasis. The oncogenic activity of YAP/TAZ is inhibited by the Hippo cascade, an evolutionarily conserved pathway that is governed by two kinases, mammalian Ste20-like kinases 1/2 (MST1/2) and Large tumor suppressor kinase 1/2 (LATS1/2), corresponding to Drosophila's Hippo (Hpo) and Warts (Wts), respectively...
February 18, 2018: Small GTPases
https://www.readbyqxmd.com/read/29448246/effect-of-mst1-on-endometriosis-apoptosis-and-migration-role-of-drp1-related-mitochondrial-fission-and-parkin-required-mitophagy
#2
Qingdong Zhao, Mingxia Ye, Wen Yang, Min Wang, Mingxia Li, Chenglei Gu, Luyang Zhao, Zhe Zhang, Weidong Han, Wensheng Fan, Yuanguang Meng
BACKGROUND/AIMS: Mitochondrial homeostasis is implicated in the development and progression of endometriosis through poorly defined mechanisms. Mst1 is the major growth suppressor related to cancer migration, apoptosis and proliferation. However, whether Mst1 is involved in endometriosis apoptosis and migration via regulating the mitochondrial function remains to be elucidated. METHODS: Expression of Mst1 in endometriosis was examined via western blots. Cellular apoptosis was detected via MTT and TUNEL assay...
February 9, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29441677/a-novel-susceptibility-locus-in-mst1-and-gene-gene-interaction-network-for-crohn-s-disease-in-the-chinese-population
#3
William K K Wu, Rui Sun, Tao Zuo, Yuanyuan Tian, Zhirong Zeng, Jeffery Ho, Justin C Y Wu, Francis K L Chan, Matthew T V Chan, Jun Yu, Joseph J Y Sung, Sunny H Wong, Maggie H Wang, Siew C Ng
The incidence of Crohn's disease is increasing in many Asian countries, but considerable differences in genetic susceptibility have been reported between Western and Asian populations. This study aimed to fine-map 23 previously reported Crohn's disease genes and identify their interactions in the Chinese population by Illumina-based targeted capture sequencing. Our results showed that the genetic polymorphism A>G at rs144982232 in MST1 showed the most significant association (P = 1.78 × 10-5; odds ratio = 4...
February 14, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29429151/the-role-of-hippo-pathway-in-cancer-stem-cell-biology
#4
Jae Hyung Park, Ji Eun Shin, Hyun Woo Park
The biological significance and deregulation of the Hippo pathway during organ growth and tumorigenesis have received a surge of interest in the past decade. The Hippo pathway core kinases, MST1/2 and LATS1/2, are tumor suppressors that inhibit the oncogenic nuclear function of YAP/TAZ and TEAD. In addition to earlier studies that highlight the role of Hippo pathway in organ size control, cell proliferation, and tumor development, recent evidence demonstrates its critical role in cancer stem cell biology, including EMT, drug resistance, and self-renewal...
February 5, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29406244/vitexin-protects-isoproterenol-induced-post-myocardial-injury-by-modulating-hipposignaling-and-er-stress-responses
#5
Rathinavel Ashokkumar, Sankar Jamuna, M S Sakeena Sadullah, S Niranjali Devaraj
The molecular mechanisms involved in ER stress-induced post myocardial injury remain elusive. In this study, we have investigated the molecular mechanism of ER stress-mediated myocyte death in Isoproterenol (ISO) induced myocardial infarction and its inhibition by a potent anti oxidant and anti-apoptotic bioflavonoid, Vitexin. ISO mediated apoptosis was found to be associated with ER permeabilization and characterized by enhanced production of ROS, activation of caspase-3, modulation of Bcl2 family proteins and activation of bnip3...
February 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29376873/lentivirus-mediated-hdac3-inhibition-attenuates-oxidative-stress-in-appswe-ps1de9-mice
#6
Linjie Yu, Yi Liu, Yuexinzi Jin, Xiang Cao, Jian Chen, Jiali Jin, Yue Gu, Xinyu Bao, Zhuoying Ren, Yun Xu, Xiaolei Zhu
Amyloid-β (Aβ) induces a burst of oxidative stress and plays a critical role in the pathogenesis of Alzheimer's disease (AD). Our previous results have shown that histone deacetylase 3 (HDAC3) inhibition ameliorates spatial memory deficits and decreases the Aβ burden in the brains of 9-month-old APPswe/PS1dE9 (APP/PS1) mice. In this study, we investigated the role of HDAC3 inhibition in oxidative stress in vivo and in vitro models of AD. HDAC3 was detected mainly in the neurons, and HDAC3 inhibition significantly decreased reactive oxygen species generation and improved primary cortical neuron viability...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29367697/identification-of-microrna-signature-in-the-progression-of-gestational-trophoblastic-disease
#7
Jiu-Ru Zhao, Wei-Wei Cheng, Ya-Xin Wang, Mei Cai, Wei-Bin Wu, Hui-Juan Zhang
Gestational trophoblastic disease (GTD) encompasses a range of trophoblast-derived disorders. The most common type of GTD is hydatidiform mole (HM). Some of HMs can further develop into malignant gestational trophoblastic neoplasia (GTN). Aberrant expression of microRNA (miRNA) is widely reported to be involved in the initiation and progression of cancers. MiRNA expression profile also has been proved to be the useful signature for diagnosis, staging, prognosis, and response to chemotherapy. Till now, the profile of miRNA in the progression of GTD has not been determined...
January 24, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29366445/clinical-implications-of-the-hippo-yap-pathway-in-multiple-cancer-contexts
#8
Han-Byul Kim, Seung-Jae Myung
The Hippo pathway plays prominent and widespread roles in various forms of human carcinogenesis. Specifically, the Yes-associated protein (YAP), a downstream effector of the Hippo pathway, can lead to excessive cell proliferation and the inhibition of apoptosis, resulting in tumorigenesis. It was reported that the YAP is strongly elevated in multiple types of human malignancies such as breast, lung, small intestine, colon, and liver cancers. Recent work indicates that, surprisingly, Hippo signaling components' (SAV1, MST1/2, Lats1/2) mutations are virtually absent in human cancer, rendering this signaling an unlikely candidate to explain the vigorous activation of the YAP in most, if not all human tumors and an activated YAP promotes the resistance to RAF-, MAPK/ERK Kinase (MEK)-, and Epidermal growth factor receptor (EGFR)-targeted inhibitor therapy...
January 25, 2018: BMB Reports
https://www.readbyqxmd.com/read/29366442/dna-binding-partners-of-yap-taz
#9
Min-Kyu Kim, Ju-Won Jang, Suk-Chul Bae
Hippo signaling plays critical roles in regulation of tissue homeostasis, organ size, and tumorigenesis by inhibiting YES-associated protein (YAP) and PDZ-binding protein TAZ through MST1/2 and LATS1/2 pathway. It is also engaged in cross-talk with various other signaling pathways, including WNT, BMPs, Notch, GPCRs, and Hedgehog to further modulate activities of YAP/TAZ. Because YAP and TAZ are transcriptional coactivators that lack DNA-binding activity, both proteins must interact with DNA-binding transcription factors to regulate target gene's expression...
January 25, 2018: BMB Reports
https://www.readbyqxmd.com/read/29344656/liraglutide-suppresses-proliferation-and-induces-adipogenic-differentiation-of-3t3-l1-cells-via-the-hippo-yap-signaling-pathway
#10
Yongmei Li, Jianying Du, Endong Zhu, Juanjuan Zhang, Jie Han, Wei Zhao, Bei Sun, Derun Tian
Liraglutide, as a glucagon-like peptide‑1 analogue, is used to treat type 2 diabetes mellitus and obesity. Previous findings have demonstrated the effects of liraglutide on adipogenesis; however, the underlying mechanism involved in this process remains to be elucidated. In the present study, to certify the effect of liraglutide on adipogenesis and explore the possible underlying mechanism involved in this process, preadipocyte 3T3‑L1 cells were cultured in adipocyte‑inducing medium and treated with liraglutide...
January 16, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29343826/mammalian-sterile-20-kinase-1-and-2-are-important-regulators-of-hematopoietic-stem-cells-in-stress-condition
#11
Da-Hye Lee, Tae-Shin Kim, Dongjun Lee, Dae-Sik Lim
The mammalian Hippo signaling pathway has been implicated in the self-renewal and differentiation of stem and progenitor cells. MST1 and MST2 (MST1/2) are core serine-threonine kinases in the Hippo signaling pathway, one of which, MST1, has been extensively investigated for its role in T cell and myeloid cell function. These studies have identified MST1 as a promising therapeutic target in immunological disease. However, the roles of MST1/2 in hematopoietic stem cell (HSC) function in vivo are not fully understood...
January 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339539/the-hippo-pathway-component-taz-promotes-immune-evasion-in-human-cancer-through-pd-l1
#12
Helena J Janse van Rensburg, Taha Azad, Min Ling, Yawei Hao, Brooke Snetsinger, Prem Khanal, Lori M Minassian, Charles H Graham, Michael J Rauh, Xiaolong Yang
The Hippo pathway component WW domain-containing transcription regulator 1 (TAZ) is a transcriptional co-activator and an oncogene in breast and lung cancer. Transcriptional targets of TAZ that modulate immune cell function in the tumour microenvironment are poorly understood. Here, we perform a comprehensive screen for immune-related genes regulated by TAZ and its paralog YAP using NanoString gene expression profiling. We identify the immune checkpoint molecule PD-L1 as a target of Hippo signaling. The upstream kinases of the Hippo pathway, mammalian STE20-like kinase 1 and 2 (MST1/2) and large tumour suppressor 1 and 2 (LATS1/2), suppress PD-L1 expression while TAZ and YAP enhance PD-L1 levels in breast and lung cancer cell lines...
January 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29278767/mir-183-regulates-milk-fat-metabolism-via-mst1-in-goat-mammary-epithelial-cells
#13
Zhi Chen, HuaiPing Shi, Shuang Sun, Jun Luo, Wei Zhang, Yu Hou, Juan J Loor
The nutritional value of goat milk largely depends on its fatty acid content and composition. MicroRNAs (miRNAs) are a class of RNA molecules 18-25nt in length that regulate gene expression and play crucial roles in several biological processes, including fatty acid metabolism. In this study, we analyzed the correlation between differentially expressed miRNAs in goat mammary tissue and the fatty acid composition of goat milk by using Pearson correlations. Results revealed that levels of miR-183 were highly and positively correlated with the fatty acid content in the milk...
December 23, 2017: Gene
https://www.readbyqxmd.com/read/29262338/homeostatic-control-of-hpo-mst-kinase-activity-through-autophosphorylation-dependent-recruitment-of-the-stripak-pp2a-phosphatase-complex
#14
Yonggang Zheng, Bo Liu, Li Wang, Huiyan Lei, Katiuska Daniela Pulgar Prieto, Duojia Pan
The Hippo pathway controls organ size and tissue homeostasis through a kinase cascade leading from the Ste20-like kinase Hpo (MST1/2 in mammals) to the transcriptional coactivator Yki (YAP/TAZ in mammals). Whereas previous studies have uncovered positive and negative regulators of Hpo/MST, how they are integrated to maintain signaling homeostasis remains poorly understood. Here, we identify a self-restricting mechanism whereby autophosphorylation of an unstructured linker in Hpo/MST creates docking sites for the STRIPAK PP2A phosphatase complex to inactivate Hpo/MST...
December 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/29259009/loss-of-rassf4-expression-in-multiple-myeloma-promotes-ras-driven-malignant-progression
#15
Eva De Smedt, Ken Maes, Stefaan Verhulst, Hui Liu, Alboukadel Kassambara, Anke Maes, Nicolas Robert, Carlo Heirman, Andrew Cakana, Dirk Hose, Karine Breckpot, Leo A van Grunsven, Kim De Veirman, Eline Menu, Karin Vanderkerken, Jerome Moreaux, Elke De Bruyne
RAS mutations occur frequently in multiple myeloma (MM), but apart from driving progression they can also stimulate antitumor effects by activating tumor suppressive RASSF proteins. While this family of death effector molecules are often silenced in cancers, functional data about RASSF proteins in MM are lacking. Here we report that RASSF4 is downregulated during MM progression and correlates with a poor prognosis. Promoter methylation analysis in human cell lines revealed an inverse correlation between RASSF4 mRNA levels and methylation status...
December 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/29222344/trip6-inhibits-hippo-signaling-in-response-to-tension-at-adherens-junctions
#16
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
#17
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/29214772/pseudolaric-acid-b-inhibits-proliferation-invasion-and-epithelial-to-mesenchymal-transition-in-human-pancreatic-cancer-cell
#18
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/29209784/acaxl2-and-acmst1-regulate-arthrospore-development-and-stress-resistance-in-the-cephalosporin-c-producer-acremonium-chrysogenum
#19
Janina Kluge, Ulrich Kück
The filamentous fungus Acremonium chrysogenum is the primordial producer of the β-lactam antibiotic cephalosporin C. This antibiotic is of major biotechnological and medical relevance because of its antibacterial activity against Gram-positive and Gram-negative bacteria. Antibiotic production during the lag phase of fermentation is often accompanied by a typical morphological feature of A. chrysogenum, the fragmentation of the mycelium into arthrospores. Here, we sought to identify factors that regulate the hyphal septation process and present the first comparative functional characterization of the type I integral plasma membrane protein Axl2 (axial budding pattern protein 2), a central component of the bud site selection system (BSSS) and Mst1 (mammalian Sterile20-like kinase), a septation initiation network (SIN)-associated germinal center kinase (GCK)...
December 5, 2017: Current Genetics
https://www.readbyqxmd.com/read/29195393/1-%C3%AE-s-broadband-frequency-sweeping-reflectometry-for-plasma-density-and-fluctuation-profile-measurements
#20
F Clairet, C Bottereau, A Medvedeva, D Molina, G D Conway, A Silva, U Stroth
Frequency swept reflectometry has reached the symbolic value of 1 μs sweeping time; this performance has been made possible, thanks to an improved control of the ramp voltage driving the frequency source. In parallel, the memory depth of the acquisition system has been upgraded and can provide up to 200 000 signals during a plasma discharge. Additional improvements regarding the trigger delay determination of the acquisition and the voltage ramp linearity required by this ultra-fast technique have been set...
November 2017: Review of Scientific Instruments
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