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https://www.readbyqxmd.com/read/29325286/-research-advances-in-the-role-of-the-hippo-yap-taz-signaling-pathway-in-primary-liver-cancer
#1
L W Guo, G L Shao
The Hippo-YAP/TAZ signaling pathway is an evolutionarily conserved pathway, which has been confirmed to play an important role in organ volume control, stem cell function, tissue regeneration, and tumorigenesis. Recent research findings show that the Hippo-YAP/TAZ signaling pathway is closely associated with the development and progression of primary liver cancer, and inhibition of the activity of this pathway may be a new method for the treatment of liver cancer. This article reviews the research advances in the role of the Hippo-YAP/TAZ signaling pathway in primary liver cancer...
November 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/29316729/wnt-rspo-and-hippo-signalling-in-the-intestine-and-intestinal-stem-cells
#2
REVIEW
Vitezslav Kriz, Vladimir Korinek
In this review, we address aspects of Wnt, R-Spondin (RSPO) and Hippo signalling, in both healthy and transformed intestinal epithelium. In intestinal stem cells (ISCs), the Wnt pathway is essential for intestinal crypt formation and renewal, whereas RSPO-mediated signalling mainly affects ISC numbers. In human colorectal cancer (CRC), aberrant Wnt signalling is the driving mechanism initiating this type of neoplasia. The signalling role of the RSPO-binding transmembrane proteins, the leucine-rich-repeat-containing G-protein-coupled receptors (LGRs), is possibly more pleiotropic and not only limited to the enhancement of Wnt signalling...
January 8, 2018: Genes
https://www.readbyqxmd.com/read/29305368/treatment-of-a-complex-orthopaedic-infection-due-to-extensively-drug-resistant-pseudomonas-aeruginosa
#3
Sidra Hassan, Mani D Kahn, Nidhi Saraiya, Priya Nori
According to the Centers for Disease Control and Prevention (CDC), approximately 51 000 healthcare-associated infections caused by Pseudomonas aeruginosa occur annually in the USA, more than 6000 of which (13%) are caused by multidrug resistant (MDR) strains. Ceftolozane/tazobactam (TOL/TAZ) (Zerbaxa) was approved by the US Food and Drug Administration (FDA) in December 2014 for the treatment of complicated intra-abdominal and urinary tract infections. At this time, clinical data on the role of TOL/TAZ treatment outside of FDA-approved indications is limited...
January 5, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29305295/the-hippo-pathway-in-normal-development-and-cancer
#4
REVIEW
Marcello Maugeri-Saccà, Ruggero De Maria
The Hippo pathway is a central regulator of organ size and tissue homeostasis. Hippo kinases and adaptor proteins mediate the phosphorylation and inactivation of YAP and TAZ, two closely related transcription co-activators. The Hippo pathway responds to a variety of extracellular and intracellular signals, spanning from cell-cell contact and mechanical cues to ligands of G-protein-coupled receptors and metabolic avenues. In some instances, YAP/TAZ activation is tuned by forces that bypass the Hippo kinase module, adding further complexity to the biology of the pathway...
January 2, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29304343/think-about-the-environment-cellular-reprogramming-by-the-extracellular-matrix
#5
David J Huels, Jan Paul Medema
In this issue of Cell Stem Cell, Yui et al. (2018) show how tissue regeneration is driven by changes in the microenvironment. During intestinal regeneration, the epithelium is reprogrammed into a fetal state by an altered extracellular matrix (ECM), which is dependent on YAP/TAZ activation.
January 4, 2018: Cell Stem Cell
https://www.readbyqxmd.com/read/29303509/hippo-pathway-coactivators-yap-and-taz-are-required-to-coordinate-mammalian-liver-regeneration
#6
Li Lu, Milton J Finegold, Randy L Johnson
The mammalian liver has a remarkable capacity for repair following injury. Removal of up to two-third of liver mass results in a series of events that include extracellular matrix remodeling, coordinated hepatic cell cycle re-entry, restoration of liver mass and tissue remodeling to return the damaged liver to its normal state. Although there has been considerable advancement of our knowledge concerning the regenerative capacity of the mammalian liver, many outstanding questions remaining, such as: how does the regenerating liver stop proliferating when appropriate mass is restored and how do these mechanisms relate to normal regulation of organ size during development? Hippo pathway has been proposed to be central in mediating both events: organ size control during development and following regeneration...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29299145/inhibition-of-yap-function-overcomes-braf-inhibitor-resistance-in-melanoma-cancer-stem-cells
#7
Matthew L Fisher, Daniel Grun, Gautam Adhikary, Wen Xu, Richard L Eckert
Treating BRAF inhibitor-resistant melanoma is an important therapeutic goal. Thus, it is important to identify and target mechanisms of resistance to improve therapy. The YAP1 and TAZ proteins of the Hippo signaling pathway are important drivers of cancer cell survival, and are BRAF inhibitor resistant factors in melanoma. We examine the role of YAP1/TAZ in melanoma cancer stem cells (MCS cells). We demonstrate that YAP1, TAZ and TEAD (TEA domain transcription factor) levels are elevated in BRAF inhibitor resistant MCS cells and enhance cell survival, spheroid formation, matrigel invasion and tumor formation...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29298862/deregulation-of-hippo-taz-pathway-during-renal-injury-confers-a-fibrotic-maladaptive-phenotype
#8
Sandybell Anorga, Jessica M Overstreet, Lucas L Falke, Jiaqi Tang, Roel G Goldschmeding, Paul J Higgins, Rohan Samarakoon
Although yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), nuclear transducers of the Hippo pathway, are mostly silent in adult organs, aberrant activation of YAP/TAZ promotes tumorigenesis and abnormal tissue repair. The extent of involvement of TAZ in chronic kidney disease (CKD) is unknown. In our study, increased TAZ nuclear accumulation and expression in the tubulointerstitium was readily evident in 3 models of renal injury including obstructive, aristolochic acid (AA), and diabetic nephropathy, correlating with fibrosis progression...
January 3, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29295700/physical-cues-drive-chondrogenic-differentiation
#9
Qi Zhang, Shiyu Lin, Jinfeng Liao, Xiaoxiao Cai
BACKGROUND: Cellular differentiation occurs in a complicated microenvironment containing multiple components including soluble factors and physical cues. In addition to biochemical composition, physical cues are also crucial in determining cellular behaviors. OBJECTIVE: To better understand the interaction between physical signals and cells, we discuss the effects of physical cues on cellular behaviors, especially chondrogenic differentiation in vitro. Furthermore, the mechanisms by which these physical signals are transmitted from the extracellular matrix into the cell are also considered...
January 2, 2018: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29286147/mutual-regulation-of-the-hippo-wnt-lpa-tgf%C3%A2-%C3%AE-signaling-pathways-and-their-roles-in-glaucoma-review
#10
Xin Wang, Guoli Huai, Hailian Wang, Yuande Liu, Ping Qi, Wei Shi, Jie Peng, Hongji Yang, Shaoping Deng, Yi Wang
Glaucoma is the leading cause of irreversible blindness worldwide and there is no effective treatment thus far. The trabecular meshwork has been identified as the major pathological area involved. Certain signaling pathways in the trabecular meshwork, including the Wnt, lysophosphatidic acid and transforming growth factor‑β pathways, have been identified as novel therapeutic targets in glaucoma treatment. Meanwhile, it has been reported that key proteins in these pathways, particularly the primary transcription regulator Yes‑associated protein (YAP) and transcriptional co‑activator with PDZ‑binding motif (TAZ), exhibit interactions with the Hippo pathway...
December 29, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29282206/colonic-epithelium-rejuvenation-through-yap-taz
#11
Rui Chen, Kun-Liang Guan
No abstract text is available yet for this article.
December 27, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29262338/homeostatic-control-of-hpo-mst-kinase-activity-through-autophosphorylation-dependent-recruitment-of-the-stripak-pp2a-phosphatase-complex
#12
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/29249622/differential-expression-of-nf2-in-neuroepithelial-compartments-is-necessary-for-mammalian-eye-development
#13
Kyeong Hwan Moon, Hyoung-Tai Kim, Dahye Lee, Mahesh B Rao, Edward M Levine, Dae-Sik Lim, Jin Woo Kim
The optic neuroepithelial continuum of vertebrate eye develops into three differentially growing compartments: the retina, the ciliary margin (CM), and the retinal pigment epithelium (RPE). Neurofibromin 2 (Nf2) is strongly expressed in slowly expanding RPE and CM compartments, and the loss of mouse Nf2 causes hyperplasia in these compartments, replicating the ocular abnormalities seen in human NF2 patients. The hyperplastic ocular phenotypes were largely suppressed by heterozygous deletion of Yap and Taz, key targets of the Nf2-Hippo signaling pathway...
December 12, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29249464/yap-taz-dependent-reprogramming-of-colonic-epithelium-links-ecm-remodeling-to-tissue-regeneration
#14
Shiro Yui, Luca Azzolin, Martti Maimets, Marianne Terndrup Pedersen, Robert P Fordham, Stine L Hansen, Hjalte L Larsen, Jordi Guiu, Mariana R P Alves, Carsten F Rundsten, Jens V Johansen, Yuan Li, Chris D Madsen, Tetsuya Nakamura, Mamoru Watanabe, Ole H Nielsen, Pawel J Schweiger, Stefano Piccolo, Kim B Jensen
Tissue regeneration requires dynamic cellular adaptation to the wound environment. It is currently unclear how this is orchestrated at the cellular level and how cell fate is affected by severe tissue damage. Here we dissect cell fate transitions during colonic regeneration in a mouse dextran sulfate sodium (DSS) colitis model, and we demonstrate that the epithelium is transiently reprogrammed into a primitive state. This is characterized by de novo expression of fetal markers as well as suppression of markers for adult stem and differentiated cells...
November 28, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29238070/the-interplay-between-mutant-p53-and-the-mevalonate-pathway
#15
REVIEW
Alejandro Parrales, Elizabeth Thoenen, Tomoo Iwakuma
Missense mutations in the TP53 gene lead to accumulation of dysfunctional TP53 proteins in tumors, showing oncogenic gain-of-function (GOF) activities. Stabilization of mutant TP53 (mutp53) is required for the GOF; however, the mechanisms by which mutp53 promotes cancer progression and how mutp53 stability is regulated are not completely understood. Recent work from our laboratory has identified statins, inhibitors of the mevalonate pathway, as degraders of conformational mutp53. Specific reduction of mevalonate-5-phosphate (MVP), a metabolic intermediate in the mevalonate pathway, by statins or mevalonate kinase (MVK) knockdown triggers CHIP ubiquitin ligase-mediated degradation of conformational mutp53 by inhibiting interaction between mutp53 and DNAJA1, a Hsp40 family member...
December 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29237206/-piperacillin-tazobactam-shortage-central-restriction-and-alternative-recommendations-as-effective-antibiotic-stewardship-intervention-at-a-maximal-care-hospital
#16
Johanna Kessel, Barbara Dolff, Thomas Wichelhaus, Nils Keiner, Michael Hogardt, Claudia Reinheimer, Imke Wieters, Sebastian Harder, Volkhard A J Kempf, Christoph Stephan
Background Drug supply bottleneck is a worldwide challenge, e. g. the antibiotics Piperacillin/Tazobactam shortage in 2016/2017. The efficacy of an appropriate replacement management was evaluated at the University Hospital Frankfurt (UHF). Methods The Antibiotic-Stewardship (ABS)-Team at UHF decreed a restriction of PIP/TAZ and provided alternative antibiotic therapy recommendations during the shortage period. Consequences of this intervention on antibiotic consumption and overall costs were investigated...
December 13, 2017: Deutsche Medizinische Wochenschrift
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/29215705/activation-of-fibroblasts-by-nicotine-promotes-the-epithelial-mesenchymal-transition-and-motility-of-breast-cancer-cells
#18
Pin-Cyuan Chen, Wen-Ying Lee, Hsiang-Hsi Ling, Chia-Hsiung Cheng, Ku-Chung Chen, Cheng-Wei Lin
The tumor microenvironment plays an important role in tumor initiation and progression. It is well documented that nicotine participates in cigarette smoking-related malignancies. Previous studies focused on the effects of nicotine on tumor cells; however, the role of the microenvironment in nicotine-mediated tumorigenesis is poorly understood. Herein, we investigated the effect and molecular mechanism of nicotine on fibroblasts and its contribution to breast cancer. We found that nicotine induced the epithelial-mesenchymal transition (EMT) of breast cancer cells and promoted activation of fibroblasts...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29213086/3d-microniches-reveal-the-importance-of-cell-size-and-shape
#19
Min Bao, Jing Xie, Aigars Piruska, Wilhelm T S Huck
Geometrical cues have been shown to alter gene expression and differentiation on 2D substrates. However, little is known about how geometrical cues affect cell function in 3D. One major reason for this lack of understanding is rooted in the difficulties of controlling cell geometry in a complex 3D setting and for long periods of culture. Here, we present a robust method to control cell volume and shape of individual human mesenchymal stem cells (hMSCs) inside 3D microniches with a range of different geometries (e...
December 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29212185/hyaluronic-acid-enhances-cell-migration-and-invasion-via-the-yap1-taz-rhamm-axis-in-malignant-pleural-mesothelioma
#20
Wataru Shigeeda, Masahiko Shibazaki, Shinji Yasuhira, Tomoyuki Masuda, Tatsuo Tanita, Yuka Kaneko, Tatsuhiro Sato, Yoshitaka Sekido, Chihaya Maesawa
Most malignant mesotheliomas (MPMs) frequently show activated forms of Yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ), which transcriptionally regulates the receptor for hyaluronic acid-mediated motility (RHAMM). As RHAMM is involved in cell migration and invasion in various tumors, we speculated that hyaluronic acid (HA) in pleural fluid might affect the progression of mesothelioma by stimulating cell migration and invasion through RHAMM. The level of RHAMM expression was decreased by YAP1/TAZ knockdown, and conversely increased by forced expression of the active form of YAP1, suggesting that RHAMM was regulated by YAP1/TAZ in MPM cells...
November 7, 2017: Oncotarget
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