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https://www.readbyqxmd.com/read/28805663/yap-taz-regulates-sprouting-angiogenesis-and-vascular-barrier-maturation
#1
Jongshin Kim, Yoo Hyung Kim, Jaeryung Kim, Do Young Park, Hosung Bae, Da-Hye Lee, Kyun Hoo Kim, Seon Pyo Hong, Seung Pil Jang, Yoshiaki Kubota, Young-Guen Kwon, Dae-Sik Lim, Gou Young Koh
Angiogenesis is a multistep process that requires coordinated migration, proliferation, and junction formation of vascular endothelial cells (ECs) to form new vessel branches in response to growth stimuli. Major intracellular signaling pathways that regulate angiogenesis have been well elucidated, but key transcriptional regulators that mediate these signaling pathways and control EC behaviors are only beginning to be understood. Here, we show that YAP/TAZ, a transcriptional coactivator that acts as an end effector of Hippo signaling, is critical for sprouting angiogenesis and vascular barrier formation and maturation...
August 14, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28799225/hydrogels-with-reversible-mechanics-to-probe-dynamic-cell-microenvironments
#2
Adrianne Rosales, Sebastian L Vega, Frank W DelRio, Jason A Burdick, Kristi S Anseth
The relationship between ECM mechanics and cell behavior is dynamic, as cells remodel and respond to changes in their local environment. Most in vitro substrates are static and supraphysiologically stiff; thus, platforms with dynamic and reversible mechanical changes are needed. Here, we developed hyaluronic acid-based substrates capable of sequential photodegradation and photoinitiated crosslinking reactions to "soften" and then "stiffen" the hydrogels over a physiologically-relevant range of moduli. Reversible mechanical signaling to adhered cells was demonstrated with human mesenchymal stem cells...
August 10, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28797843/blockade-of-stearoyl-coa-desaturase-1-activity-reverts-resistance-to-cisplatin-in-lung-cancer-stem-cells
#3
Maria Elena Pisanu, Alessia Noto, Claudia De Vitis, Stefania Morrone, Giosuè Scognamiglio, Gerardo Botti, Federico Venuta, Daniele Diso, Ziga Jakopin, Fabrizio Padula, Alberto Ricci, Salvatore Mariotta, Maria Rosaria Giovagnoli, Enrico Giarnieri, Ivano Amelio, Massimiliano Agostini, Gerry Melino, Gennaro Ciliberto, Rita Mancini
Poor prognosis in lung cancer has been attributed to the presence of lung cancer stem cells (CSCs) which resist chemotherapy and cause disease recurrence. Hence, the strong need to identify mechanisms of chemoresistance and to develop new combination therapies. We have previously shown that Stearoyl-CoA-desaturase 1 (SCD1), the enzyme responsible for the conversion of saturated to monounsaturated fatty acids is upregulated in 3D lung cancer spheroids and is an upstream activator of key proliferation pathways β-catenin and YAP/TAZ...
August 7, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28793266/the-epithelial-circumferential-actin-belt-regulates-yap-taz-through-nucleocytoplasmic-shuttling-of-merlin
#4
Kana T Furukawa, Kazunari Yamashita, Natsuki Sakurai, Shigeo Ohno
Circumferential actin belts underlying the adherens junctions of columnar epithelial cell monolayers control intercellular surface tension and cell shape to maintain tissue integrity. Yes-associated protein (YAP) and its paralog TAZ are proliferation-activating transcriptional coactivators that shuttle between the nucleus and cytoplasm. Previous studies suggest the importance of stress fibers in the actin cytoskeleton for regulation of YAP nuclear localization; however, the role of the circumferential actin belt on YAP localization remains unclarified...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28782275/emerging-role-of-hippo-signalling-pathway-in-bladder-cancer
#5
REVIEW
Jianling Xia, Ming Zeng, Hua Zhu, Xiangjian Chen, Zhiliang Weng, Shi Li
Bladder cancer (BC) is one of the most common cancers worldwide with a high progression rate and poor prognosis. The Hippo signalling pathway is a conserved pathway that plays a crucial role in cellular proliferation, differentiation and apoptosis. Furthermore, dysregulation and/or malfunction of the Hippo pathway is common in various human tumours, including BC. In this review, an overview of the Hippo pathway in BC and other cancers is presented. We focus on recent data regarding the Hippo pathway, its network and the regulation of the downstream co-effectors YAP1/TAZ...
August 7, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28768710/yap-taz-deletion-in-gli-cell-derived-myofibroblasts-attenuates-fibrosis
#6
Ming Liang, Michael Yu, Ruohan Xia, Ke Song, Jun Wang, Jinlong Luo, Guang Chen, Jizhong Cheng
In damaged kidneys, increased extracellular matrix (ECM) and tissue stiffness stimulate kidney fibrosis through incompletely characterized molecular mechanisms. The transcriptional coactivators yes-associated protein (Yap) and transcriptional coactivator with PDZ-binding motif (Taz) function as mechanosensors in cancer cells and have been implicated in the regulation of myofibroblasts in the kidney. We hypothesized that the development of kidney fibrosis depends on Yap-induced activation and proliferation of kidney fibroblasts...
August 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28767425/usp21-regulates-hippo-pathway-activity-by-mediating-mark-protein-turnover
#7
Hung Thanh Nguyen, Jan-Michael Kugler, Anand C Loya, Stephen M Cohen
The Hippo pathway, which acts to repress the activity of YAP and TAZ trancriptional co-activators, serve as a barrier for oncogenic transformation. Unlike other oncoproteins, YAP and TAZ are rarely activated by mutations or amplified in cancer. However, elevated YAP/TAZ activity is frequently observed in cancer and often correlates with worse survival. The activity and stability of Hippo pathway components, including YAP/TAZ, AMOT and LATS1/2, are regulated by ubiquitin-mediated protein degradation. Aberrant expression of ubiquitin ligase complexes that regulate the turnover of Hippo components and deubiquitylating enzymes that counteract these ubiquitin ligases have been implicated in human cancer...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28763902/-role-of-yes-associated-protein-1-in-angiotensin%C3%A2-induced-pulmonary-fibrosis-in-rats
#8
M X Pan, B B Zheng, N N Sun, Z M Zheng, Q J Yang, Y Meng
Objective: To explore the mechanism of Yes-associated protein 1 (Yap1) in angiotensinⅡ(AngⅡ)-induced pulmonary fibrosis. Methods:In vivo, 18 male Wistar rats were randomly divided into three equal groups with 6 rats in each group, including control group, bleomycin-treated group (BLM), and BLM+ AngⅡ group. 28 days later, the lung tissues in all groups were harvested for the HE and Masson staining as well as the immunohistochemical (IHC) staining for Yap1. In vitro, the isolated fibroblasts were treated with 10(-7) mmol/L AngⅡor the AngⅡ-targeted inhibitor irbesartan for the scheduled time for mRNA and protein expressions of Yap1, PDZ-binding motif (TAZ), and collagen Ⅰusing PCR and Western blot, as well as the translocation test from the nucleus to the cytoplasm of Yap1 and TAZ...
July 25, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28757477/the-roles-and-mechanisms-of-the-hippo-yap-signaling-pathway-in-the-nervous-system
#9
Bao Xiaomei, He Qing, Wang Ying, Huang Zhihui, Yuan Zengqiang
The Hippo signaling pathway, consisting of a highly conserved kinase cascade and downstream transcription co-activators YAP (Yes-associated protein)/TAZ (transcriptional coactivator with PDZ-binding motif), plays a key role in tissue homeostasis and organ size control by regulating the proliferation, differentiation and apoptosis of cells. During normal development, the precise control of neural cell numbers and spatial distributions of these neural cells is important for brain development. Recent studies have shown that the Hippo/YAP signaling pathway is actively involved in the self-renewal of neural stem cells, proliferation of neural progenitor cells, differentiation and activation of glial cells, and myelination of glial cells as well as in the development of neurological diseases...
July 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28757476/the-regulatory-mechanisms-and-functional-roles-of-the-hippo-signaling-pathway-in-breast-cancer
#10
Yao Chuanbo, Zhou Xin, Chen Ceshi, Lei Qunying
Hippo signaling pathway has attracted broad attention due to its essential roles in controlling organ size and tumorigenesis. TAZ/YAP, two core downstream molecules of the Hippo signaling pathway in mammals, are tightly regulated by a wide range of extracellular and intrinsic signals in both Hippo signaling pathway-dependent and -independent manners. Besides their roles in the development and function of normal mammary glands, TAZ/YAP display remarkable potency and relevance to multiple aspects of human breast carcinogenesis, including cellular proliferation, differentiation, apoptosis, migration, invasion, epithelial-mesenchymal transition and stemness...
July 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28757474/hippo-signaling-pathway-in-lung-development-regeneration-and-diseases
#11
Fu Siling, Zhao Wanying, Zhang Wenjing, Song Hai, Ji Hongbin, Tang Nan
function between the circulation and the atmospheric environment. Lung diseases, including lung cancer, are among the leading causes of death in the modern society. Research on lung development, regeneration and cancer could provide significant insights for the development of therapeutic approaches on lung diseases. Hippo/YAP/TAZ signaling pathway regulates cell proliferation and differentiation, controls organ size, and plays an important role in response to mechanical forces. YAP/TAZ are expressed in many cell types and serve various regulatory functions in the embryonic and adult lungs...
July 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28757470/molecular-mechanisms-of-the-mammalian-hippo-signaling-pathway
#12
Ji Xinyan, Zhong Guoxuan, Zhao Bin
The Hippo pathway plays an evolutionarily conserved fundamental role in controlling organ size in multicellular organisms. Importantly, evidence from studies of patient samples and mouse models clearly indicates that deregulation of the Hippo signaling pathway plays a crucial role in the initiation and progression of many different types of human cancers. The Hippo signaling pathway is regulated by various stimuli, such as mechanical stress, G-protein coupled receptor signaling, and cellular energy status. When activated, the Hippo kinase cascade phosphorylates and inhibits the transcription co-activator YAP (Yes-associated protein), and its paralog TAZ (transcriptional coactivator with PDZ-binding motif), resulting in their cytoplasmic retention and degradation...
July 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28757164/surface-topography-guides-morphology-and-spatial-patterning-of-induced-pluripotent-stem-cell-colonies
#13
Giulio Abagnale, Antonio Sechi, Michael Steger, Qihui Zhou, Chao-Chung Kuo, Gülcan Aydin, Carmen Schalla, Gerhard Müller-Newen, Martin Zenke, Ivan G Costa, Patrick van Rijn, Arnold Gillner, Wolfgang Wagner
The relevance of topographic cues for commitment of induced pluripotent stem cells (iPSCs) is largely unknown. In this study, we demonstrate that groove-ridge structures with a periodicity in the submicrometer range induce elongation of iPSC colonies, guide the orientation of apical actin fibers, and direct the polarity of cell division. Elongation of iPSC colonies impacts also on their intrinsic molecular patterning, which seems to be orchestrated from the rim of the colonies. BMP4-induced differentiation is enhanced in elongated colonies, and the submicron grooves impact on the spatial modulation of YAP activity upon induction with this morphogen...
August 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28756314/incorporating-twitter-based-human-activity-information-in-spatial-analysis-of-crashes-in-urban-areas
#14
Jie Bao, Pan Liu, Hao Yu, Chengcheng Xu
The primary objective of this study was to investigate how to incorporate human activity information in spatial analysis of crashes in urban areas using Twitter check-in data. This study used the data collected from the City of Los Angeles in the United States to illustrate the procedure. The following five types of data were collected: crash data, human activity data, traditional traffic exposure variables, road network attributes and social-demographic data. A web crawler by Python was developed to collect the venue type information from the Twitter check-in data automatically...
July 27, 2017: Accident; Analysis and Prevention
https://www.readbyqxmd.com/read/28754668/transglutaminase-2-inhibition-reverses-mesenchymal-transdifferentiation-of-glioma-stem-cells-by-regulating-c-ebp%C3%AE-signaling
#15
Jinlong Yin, Young Taek Oh, Jeong-Yub Kim, Sung Soo Kim, Eunji Choi, Tae Hoon Kim, Jun Hee Hong, Nakho Chang, Hee Jin Cho, Jason Kyungha Sa, Jeong Cheol Kim, Hyung Joon Kwon, Saewhan Park, Weiwei Lin, Ichiro Nakano, Ho-Shin Gwak, Heon Yoo, Seung-Hoon Lee, Jeongwu Lee, Jong Heon Kim, Soo-Youl Kim, Do-Hyun Nam, Myung-Jin Park, Jong Bae Park
Necrosis is a hallmark of glioblastoma (GBM) and is responsible for poor prognosis and resistance to conventional therapies. However, the molecular mechanisms underlying necrotic microenvironment-induced malignancy of GBM have not been elucidated. Here, we report that transglutaminase 2 (TGM2) is upregulated in the perinecrotic region of GBM and triggered mesenchymal (MES) transdifferentiation of glioma stem cells (GSC) by regulating master transcription factors (TF), such as C/EBPβ, TAZ, and STAT3. TGM2 expression was induced by macrophages/microglia-derived cytokines via NFκB activation and further degraded DNA damage-inducible transcript 3 (GADD153) to induce C/EBPβ expression, resulting in expression of the MES transcriptome...
July 28, 2017: Cancer Research
https://www.readbyqxmd.com/read/28752853/regulation-of-hippo-pathway-transcription-factor-tead-by-p38-mapk-induced-cytoplasmic-translocation
#16
Kimberly C Lin, Toshiro Moroishi, Zhipeng Meng, Han-Sol Jeong, Steven W Plouffe, Yoshitaka Sekido, Jiahuai Han, Hyun Woo Park, Kun-Liang Guan
The Hippo pathway controls organ size and tissue homeostasis, with deregulation leading to cancer. The core Hippo components in mammals are composed of the upstream serine/threonine kinases Mst1/2, MAPK4Ks and Lats1/2. Inactivation of these upstream kinases leads to dephosphorylation, stabilization, nuclear translocation and thus activation of the major functional transducers of the Hippo pathway, YAP and its paralogue TAZ. YAP/TAZ are transcription co-activators that regulate gene expression primarily through interaction with the TEA domain DNA-binding family of transcription factors (TEAD)...
July 28, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28749195/hippo-pathway-contributes-to-cisplatin-resistant-induced-emt-in-nasopharyngeal-carcinoma-cells
#17
Shuo Li, Xiaomeng Zhang, Rongkai Zhang, Zibin Liang, Wei Liao, Zhengde Du, Chunsheng Gao, Fei Liu, Yunping Fan, Haiyu Hong
Nasopharyngeal carcinoma (NPC) is a kind of head-neck malignant tumor derived from the nasopharyngeal epithelium and is mainly prevalent in Southern China and Southeast Asia countries. Cisplatin (DDP) provides the first-line therapeutic administration in NPC patients. However, chemoresistance has been a main barrier and caused bad treatment outcome in NPC therapy. To understand the molecular mechanism of acquired resistance to DDP, multiple methods were performed to examine the morphocytology and molecular changes in DDP-resistant NPC cells...
July 27, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28740772/relationship-between-keloid-formation-and-yap-taz-signaling
#18
Noriko Aramaki-Hattori, Keisuke Okabe, Mariko Hamada, Tamae Takato, Kazuo Kishi
YAP (yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are part of a classical pathway that controls contact inhibition in the Hippo pathway. YAP and TAZ were recently reported to act as nuclear relays of mechanical signals that communicate extracellular matrix rigidity and cell shape. However, the role of YAP/TAZ signaling in keloid formation is unclear. Here, we used immunohistochemistry to investigate YAP/TAZ expression in keloid and nonaffected lesions. YAP/TAZ expression in keloid fibroblasts had a greater tendency to localize to the nucleus relative to that seen in fibroblasts from unaffected tissues...
June 2017: Plastic and Reconstructive Surgery. Global Open
https://www.readbyqxmd.com/read/28739802/tgf-%C3%AE-1-regulates-the-expression-and-transcriptional-activity-of-taz-via-a-smad3-independent-myocardin-related-transcription-factor-mediated-mechanism
#19
Maria Zena Miranda, Janne Folke Bialik, Pam Speight, Qinghong Dan, Tony Yeung, Katalin Szászi, Stine F Pedersen, András Kapus
Hippo pathway transcriptional coactivators TAZ and YAP and the TGF-β1 (TGFβ) effector Smad3 regulate a common set of genes, can physically interact and exhibit multilevel crosstalk regulating cell fate-determining and fibrogenic pathways. However, a key aspect of this crosstalk, TGFβ-mediated regulation of TAZ or YAP expression remains uncharacterized. Here, we show that TGFβ induces robust TAZ but not YAP protein expression in both mesenchymal and epithelial cells. TAZ levels, and to a lesser extent YAP levels, also increased during experimental kidney fibrosis...
July 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28737828/taz-inhibition-restores-sensitivity-of-cisplatin-via-akt-mtor-signaling-in-lung-adenocarcinoma
#20
Wei Xu, Yunyan Wei, Yue Li, Yuan Yin, Weiwei Yuan, Yan Yang, Weihong Zhao, Jianqing Wu
The cisplatin-based doublet remains the foundation of treatment for the majority of patients with advanced non-small cell lung cancer (NSCLC), however, many patients exhibit acquired drug resistance. Transcriptional co-activator with PDZ binding motif (TAZ) is an oncogene in lung cancer, important for lung tumorigenesis and metastasis. Recently, it was revealed that TAZ upregulation confers resistance against a diverse range of cytotoxic agents. The present study aimed to investigate whether TAZ is involved in cisplatin sensitivity in lung adenocarcinoma...
July 24, 2017: Oncology Reports
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