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Hippo signalling

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https://www.readbyqxmd.com/read/28718798/co-expression-network-and-pathway-analyses-reveal-important-modules-of-mirnas-regulating-milk-yield-and-component-traits
#1
Duy N Do, Pier-Luc Dudemaine, Ran Li, Eveline M Ibeagha-Awemu
Co-expression network analyses provide insights into the molecular interactions underlying complex traits and diseases. In this study, co-expression network analysis was performed to detect expression patterns (modules or clusters) of microRNAs (miRNAs) during lactation, and to identify miRNA regulatory mechanisms for milk yield and component traits (fat, protein, somatic cell count (SCC), lactose, and milk urea nitrogen (MUN)) via miRNA target gene enrichment analysis. miRNA expression (713 miRNAs), and milk yield and components (Fat%, Protein%, lactose, SCC, MUN) data of nine cows at each of six different time points (day 30 (D30), D70, D130, D170, D230 and D290) of an entire lactation curve were used...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28700256/hippo-pathway-an-emerging-regulator-of-craniofacial-and-dental-development
#2
J Wang, J F Martin
The evolutionarily conserved Hippo signaling pathway is a vital regulator of organ size that fine-tunes cell proliferation, apoptosis, and differentiation. A number of important studies have revealed critical roles of Hippo signaling and its effectors Yap (Yes-associated protein) and Taz (transcriptional coactivator with PDZ binding motif) in tissue development, homeostasis, and regeneration, as well as in tumorigenesis. In addition, recent studies have shown evidence of crosstalk between the Hippo pathway and other key signaling pathways, such as Wnt signaling, that not only regulates developmental processes but also contributes to disease pathogenesis...
July 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28698384/palmitic-acid-dysregulates-the-hippo-yap-pathway-and-inhibits-angiogenesis-by-inducing-mitochondrial-damage-and-activating-the-cytosolic-dna-sensor-cgas-sting-irf3-signaling
#3
Liangshuai Yuan, Yun Mao, Wei Luo, Weiwei Wu, Hao Xu, Xing Li Wang, Ying H Shen
Impaired angiogenesis and wound healing carry significant morbidity and mortality in diabetic patients. Metabolic stress from hyperglycemia and elevated free fatty acids have been shown to inhibit endothelial angiogenesis. However, the underlying mechanisms remain poorly understood. In this study, we show that dysregulation of the Hippo-YAP pathway, an important signaling in regulating tissue repair and regeneration, underlies palmitic acid (PA) -induced inhibition of endothelial angiogenesis. PA inhibited endothelial cell proliferation, migration and tube formation, which were associated with increased MST1 expression, YAP phosphorylation/inactivation and nuclear exclusion...
July 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28697337/basement-membrane-manipulation-in-drosophila-wing-discs-affects-dpp-retention-but-not-growth-mechanoregulation
#4
Mengqi Ma, Xueya Cao, Jianli Dai, José C Pastor-Pareja
Basement membranes (BMs) are extracellular matrix polymers basally underlying epithelia, where they regulate cell signaling and tissue mechanics. Constriction by the BM shapes Drosophila wing discs, a well-characterized model of tissue growth. Recently, the hypothesis that mechanical factors govern wing growth has received much attention, but it has not been definitively tested. In this study, we manipulated BM composition to cause dramatic changes in tissue tension. We found that increased tissue compression when perlecan was knocked down did not affect adult wing size...
July 10, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28686611/yorkie-is-required-to-restrict-the-injury-responses-in-planarians
#5
Alexander Y T Lin, Bret J Pearson
Regeneration requires the precise integration of cues that initiate proliferation, direct differentiation, and ultimately re-pattern tissues to the proper size and scale. Yet how these processes are integrated with wounding responses remains relatively unknown. The freshwater planarian, Schmidtea mediterranea, is an ideal model to study the stereotyped proliferative and transcriptional responses to injury due to its high capacity for regeneration. Here, we characterize the effector of the Hippo signalling cascade, yorkie, during planarian regeneration and its role in restricting early injury responses...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28684311/hippo-effector-yap-directly-regulates-the-expression-of-pd-l1-transcripts-in-egfr-tki-resistant-lung-adenocarcinoma
#6
Byung Soo Lee, Dong Il Park, Da Hye Lee, Jeong Eun Lee, Min-Kyung Yeo, Yeon Hee Park, Dae Sik Lim, Wonyoung Choi, Da Hye Lee, Geon Yoo, Han-Byul Kim, Dahyun Kang, Jae Young Moon, Sung Soo Jung, Ju Ock Kim, Hee Sun Park, Chaeuk Chung
Developments of EGFR-TKI and immunotherapy targeting the PD1/PD-L1 pathway are considered most important medical breakthroughs in lung cancer treatment. Nowadays, 3rd generation EGFR TKI is widely used for T790M positive 1st and 2nd EGFR-TKI resistant lung cancer patients. Immunotherapy is powerful option for lung cancer patients without drug targets and chemotherapy resistant patients. It also has changed the concept of conventional anti-cancer therapy in the point of regulating tumor microenvironment. There are many studies linking these two important pathways...
July 3, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28682834/high-expression-of-yes-activated-protein-1-in-papillary-thyroid-carcinoma-correlates-with-poor-prognosis
#7
Zeming Liu, Wen Zeng, Yusufu Maimaiti, Jie Ming, Yawen Guo, Yan Liu, Chunping Liu, Tao Huang
CONTEXT: The Hippo signal transduction pathway is highly conserved in mammals. It plays a critical role in tissue and organ size by regulating the balance between cell proliferation and apoptosis. However, there have been few reports concerning Yes-activated protein-1 (YAP-1) elevation in papillary thyroid cancer (PTC). OBJECTIVE: The objective of this study was to determine whether YAP-1 expression is a biomarker and high-risk clinicopathologic prognosticator in PTC...
July 4, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28677804/mapk-and-hippo-signaling-pathways-crosstalk-via-the-raf-1-mst-2-interaction-in-malignant-melanoma
#8
Ruizheng Feng, Junsheng Gong, Lina Wu, Lei Wang, Baolin Zhang, Gang Liang, Huixia Zheng, Hong Xiao
The aim of the present study was to expound on the interactions between the mitogen-activated protein kinase (MAPK) and Hippo pathway members, and to further elucidate the molecular mechanisms of melanoma tumorigenesis. Four melanoma cell lines (C32, HS695T, SK-MEL-28 and A375) were used in the present study. Western blotting was used to assess the expression levels of the MAPK and Hippo pathway effector proteins: rapidly accelerated fibrosarcoma-1 proto-oncogene, serine/threonine kinase (RAF-1); serine/threonine kinase 3 (STK3; also known as MST-2); yes-associated protein (YAP); and tafazzin (TAZ)...
June 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28673931/mechanical-cue-induced-yap-instructs-skp2-dependent-cell-cycle-exit-and-oncogenic-signaling
#9
Wonyul Jang, Tackhoon Kim, Ja Seung Koo, Sang-Kyum Kim, Dae-Sik Lim
Mechanical tensions are usually generated during development at spatially defined regions within tissues. Such physical cues dictate the cellular decisions of proliferation or cell cycle arrest. Yet, the mechanisms by which mechanical stress controls the cell cycle are not yet fully understood. Here, we report that mechanical cues function upstream of Skp2 transcription in human breast cancer cells. We found that YAP, the mechano-responsive oncogenic Hippo signaling effector, directly promotes Skp2 transcription...
July 3, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28672915/induction-of-reprogramming-of-human-amniotic-epithelial-cells-into-ips-cells-by-overexpression-of-yap-oct4-and-sox2-through-the-activation-of-the-hippo-yap-pathway
#10
Yanhui Zhao, Xinfeng Fei, Jianming Guo, Gang Zou, Weidong Pan, Jingju Zhang, Yongyi Huang, Te Liu, Weiwei Cheng
The present study has reported a novel method for producing induced pluripotent stem (iPS) cells. Primary human amniotic epithelial cells (HuAECs) were isolated from the amniotic membranes of pregnant women who received Cesarean sections. These cells were infected with retroviruses carrying octamer-binding transcription factor 4 (Oct4), (sex determining region Y)-box 2 (Sox2) and Yes-associated protein (Yap) (OSY). Following in vitro culture for ~14 days, epithelial-like HuAECs exhibited several iPS clone-like cell colonies (OSY-iPS)...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28667262/the-hippo-pathway-acts-downstream-of-the-hedgehog-signaling-to-regulate-follicle-stem-cell-maintenance-in-the-drosophila-ovary
#11
Ta-Hsing Hsu, Chia-Yu Yang, Tsung-Han Yeh, Yi-Chia Huang, Tsu-Wei Wang, Jenn-Yah Yu
The Hippo pathway is conserved and plays important roles in organ size control. The core components of the Hippo pathway are two kinases Hippo (Hpo), Warts (Wts), and a transcription-co-activator Yorkie (Yki). Yki activity is regulated by phosphorylation, which affects its nuclear localization and stability. To determine the role of the Hippo pathway in stem cells, we examine follicle stem cells (FSCs) in the Drosophila ovary. Yki is detected in the nucleus of FSCs. Knockdown of yki in the follicle cell lineage leads to a disruption of the follicular epithelium...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28661054/platelet-derived-growth-factor-regulates-yap-transcriptional-activity-via-src-family-kinase-dependent-tyrosine-phosphorylation
#12
Rory L Smoot, Nathan W Werneburg, Takaaki Sugihara, Matthew C Hernandez, Lin Yang, Christine Mehner, Rondell P Graham, Steven F Bronk, Mark J Truty, Gregory J Gores
The Hippo pathway effector YAP is implicated in the pathogenesis of cholangiocarcinoma (CCA). The Hippo pathway relies on signaling cross talk for its regulation. Given the importance of platelet derived growth factor receptor (PDGFR) signaling in CCA biology, our aim was to examine potential YAP regulation by PDGFR. We employed human and mouse CCA specimens and cell lines for these studies. Initially, we confirmed upregulation of PDGFRβ and PDGFR ligands in human and mouse CCA specimens and cell lines. YAP, a transcriptional co-activator, was localized to the nucleus in human CCA specimens and a cell line, as well as patient derived xenografts (PDX)...
June 29, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28652775/wwc3-downregulation-correlates-with-poor-prognosis-and-inhibition-of-hippo-signaling-in-human-gastric-cancer
#13
Jiabin Hou, Jin Zhou
The aim of this study was to investigate the clinicopathological significance and biological roles of WWC3 in human gastric cancer (GC). Clinical significance of WWC3 in human GCs was examined by using immunohistochemistry (IHC). WWC3 was downregulated in 48 of 111 human GCs, and its downregulation was associated with advanced stage, positive nodal status, and higher relapse rate. Importantly, WWC3 downregulation correlated with poor survival. It was also found that WWC3 protein expression was downregulated in GC cell lines compared with normal cell line GES-1...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28644919/signaling-and-epigenetic-mechanisms-of-intestinal-stem-cells-and-progenitors-insight-into-crypt-homeostasis-plasticity-and-niches
#14
REVIEW
Ryan J Smith, Abilasha Rao-Bhatia, Tae-Hee Kim
The rapid turnover of intestinal epithelial cells is maintained by a small number of stem cells located in pocket-like gland structures called crypts. While our understanding of the identity and function of intestinal stem cells (ISCs) has rapidly progressed, epigenetic and transcriptional regulation in crypt stem cell and progenitor pools remains an active field of investigation. Surrounded by various types of cells in the stroma, crypt progenitors display high levels of plasticity, harboring the ability to interconvert in the face of epithelial damage...
June 23, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28644436/the-lats1-and-lats2-tumor-suppressors-beyond-the-hippo-pathway
#15
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
#16
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
#17
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/28620131/exosomes-containing-differential-expression-of-microrna-and-mrna-in-osteosarcoma-that-can-predict-response-to-chemotherapy
#18
Ji-Feng Xu, Ya-Ping Wang, Shui-Jun Zhang, Yu Chen, Hai-Feng Gu, Xiao-Fan Dou, Bing Xia, Qing Bi, Shun-Wu Fan
A major challenge in osteosarcoma (OS) is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent. We developed a profiling strategy for serum exosomal microRNAs and mRNAs in OS patients with differential chemotherapeutic responses. Twelve miRNAs were up regulated and 18 miRNAs were under regulated significantly in OS patient with poor chemotherapeutic response when compared with those in good chemotherapeutic response (p<0...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620086/a-genetic-screen-reveals-an-unexpected-role-for-yorkie-signaling-in-jak-stat-dependent-hematopoietic-malignancies-in-drosophila-melanogaster
#19
Abigail M Anderson, Alessandro A Bailetti, Elizabeth Rodkin, Atish De, Erika A Bach
A gain-of-function mutation in the tyrosine kinase JAK2 (JAK2(V617F) ) causes human myeloproliferative neoplasms (MPNs). These patients present with high numbers of myeloid lineage cells and have numerous complications. Since current MPN therapies are not curative, there is a need to find new regulators and targets of JAK/STAT signaling that may represent additional clinical interventions. Drosophila melanogaster offers a low complexity model to study MPNs as JAK/STAT signaling is simplified with only one JAK (Hopscotch (Hop)) and one STAT (Stat92E)...
June 15, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28619819/yorkie-and-hedgehog-independently-restrict-bmp-production-in-escort-cells-to-permit-germline-differentiation-in-the-drosophila-ovary
#20
Jianhua Huang, Amy Reilein, Daniel Kalderon
Multiple signaling pathways guide the behavior and differentiation of both germline stem cells (GSCs) and somatic stem cells (FSCs) in the Drosophila germarium, necessitating careful control of signal generation, range and responses. Signal integration involves Escort Cells (ECs), which promote differentiation of the GSC derivatives they envelop, provide niche signals for FSCs and derive directly from FSCs in adults. Hedgehog (Hh) signaling induces the Hippo pathway effector Yorkie (Yki) to promote proliferation and maintenance of FSCs but Hh also signals to ECs, which are quiescent...
June 15, 2017: Development
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