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https://www.readbyqxmd.com/read/29228123/role-of-yes-associated-protein-1-angiomotin-and-mitogen-activated-kinase-kinase-1-2-in-development-of-the-bovine-blastocyst
#1
Verónica M Negrón-Pérez, Peter J Hansen
The morula-stage embryo is transformed into a blastocyst composed of epiblast, hypoblast and trophectoderm (TE) through mechanisms that, at least in the mouse, involve the Hippo signaling and mitogen-activated kinase (MAPK) pathways. Using the cow as an additional model, we tested the hypotheses that TE and hypoblast differentiation were regulated by the Hippo pathway regulators, YAP1 and AMOT, and MAPK kinase 1/2 (MAPK1/2). The presence of YAP1 and CDX2 in the nucleus and cytoplasm of MII oocytes and embryos was evaluated by immunofluorescence labeling...
December 8, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/29206651/novel-therapeutic-strategies-and-targets-in-advanced-uveal-melanoma
#2
Vivian Chua, Andrew E Aplin
PURPOSE OF REVIEW: Currently, there are no U.S. Food and Drug Administration-approved or effective treatment options for advanced-stage uveal melanoma. In this article, we focus on therapeutic targets in pathways/mechanisms associated with common mutations in uveal melanoma. We review the challenges associated with targeting of these pathways and novel treatment strategies. RECENT FINDINGS: Common mutations that promote uveal melanoma initiation and progression include alterations in G protein subunit alpha q/11 (GNAQ/GNA11) and breast cancer gene 1-associated protein 1 (BAP1)...
December 4, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29184109/activation-of-erk-in-ileal-epithelial-cells-engaged-in-ischemic-injury-repair
#3
Haruna Takeda, Etsuko Kiyokawa
Intestinal epithelial cells function as a barrier to protect our body from various agents; therefore, any damage to these cells must be immediately repaired. Several in vivo and vitro studies have shown the involvement of Erk (extracellular signal-regulated kinase) in the regeneration process; however, the spatial regulation of Erk related to tissue morphology has not been well documented. Using two-photon microscopy and mice carrying a Förster resonance energy transfer-based biosensor, we here monitored the Erk activity in the ileal epithelial cells of living mice...
November 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29175418/src-family-kinase-tyrosine-phosphorylates-toll-like-receptor-4-to-dissociate-myd88-and-mal-tirap-suppressing-lps-induced-inflammatory-responses
#4
Jonathon Mitchell, Su Jin Kim, Alexandra Seelmann, Brendan Veit, Brooke Shepard, Eunok Im, Sang Hoon Rhee
Src family kinases (SFKs) are a family of protein tyrosine kinases containing nine members: Src, Lyn, Fgr, Hck, Lck, Fyn, Blk, Yes, and Ylk. Although SFK activation is a major immediate signaling event in LPS/Toll-like receptor 4 (TLR4) signaling, its precise role has remained elusive due to various contradictory results obtained from a certain SFK member-deficient mice or cells. The observed inconsistencies may be due to the compensation or redundancy by other SFKs upon a SFK deficiency. The chemical rescuing approach was suggested to induce temporal and precise SFK activation in living cells, thereby limiting the chance of cellular adaption to a SFK-deficient condition...
November 23, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29174914/src-family-kinases-sfks-and-cell-polarity-in-the-testis
#5
REVIEW
Xiang Xiao, Ya Ni, Chenhuan Yu, Linxi Li, Baiping Mao, Yue Yang, Dongwang Zheng, Bruno Silvestrini, C Yan Cheng
Non-receptor Src family kinases (SFKs), mostly notably c-Src and c-Yes, are recently shown to be expressed by Sertoli and/or germ cells in adult rat testes. Studies have shown that SFKs are involved in modulating the cell cytoskeletal function, and involved in endocytic vesicle-mediated protein endocytosis, transcytosis and/or recycling as well as intracellular protein degradation events. Furthermore, a knockdown to SFKs, in particular c-Yes, has shown to induce defects in spermatid polarity. These findings, coupled with emerging evidence in the field, thus prompt us to critically evaluate these findings to put forth a developing concept regarding the role of SFKs and cell polarity, which will become a basis to design experiments for future investigations...
November 21, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29163769/yap1-is-essential-for-tumor-growth-and-is-a-potential-therapeutic-target-for-egfr-dependent-lung-adenocarcinomas
#6
Ting-Fang Lee, Yu-Chi Tseng, Wei-Chin Chang, Yi-Chen Chen, Yu-Rung Kao, Teh-Ying Chou, Chao-Chi Ho, Cheng-Wen Wu
Epidermal growth factor receptor (EGFR) mutations are found in lung adenocarcinomas leading to tumor cells proliferation and survival. EGFR tyrosine kinase inhibitors (TKIs) that block EGFR activity are effective therapeutics for EGFR-mutant lung adenocarcinoma patients, but TKI-resistance inevitably occurs. The YES-associated protein (YAP1) transcription coactivator has been implicated as an oncogene and is amplified in human cancers and provides tumor cells strong proliferation and survival cues. This study investigated the roles of YAP1 in lung adenocarcinoma by exploring its regulation and functions mediated by EGFR signaling...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155025/understanding-the-role-of-mammalian-sterile-20-like-kinase-1-mst1-in-cardiovascular-disorders
#7
REVIEW
Yang Yang, Haichang Wang, Zhiqiang Ma, Wei Hu, Dongdong Sun
Hippo signaling is a conserved pathway and plays important role in controlling cell proliferation and differentiation. As critical components of the Hippo pathway in mammals, mammalian sterile 20-like kinase 1 (MST1) participate in cell apoptosis and cell proliferation. Yes-associated protein (YAP) acts as a downstream transcriptional co-activator of MST1. MST1 is present in heart tissue and helps determine the fate of cardiomyocytes by regulating the balance between autophagy and apoptosis. Recent studies showed MST1 signaling is an essential participant in many cardiovascular disorders, including aortic dissection, aortic aneurysm, atherosclerosis, myocardial ischemic injury, and cardiomyopathy...
November 15, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29136529/yap-dependent-axl-overexpression-mediates-resistance-to-egfr-inhibitors-in-nsclc
#8
Elena Ghiso, Cristina Migliore, Vito Ciciriello, Elena Morando, Annalisa Petrelli, Simona Corso, Emmanuele De Luca, Gaia Gatti, Marco Volante, Silvia Giordano
The Yes-associated protein (YAP) is a transcriptional co-activator upregulating genes that promote cell growth and inhibit apoptosis. The main dysregulation of the Hippo pathway in tumors is due to YAP overexpression, promoting epithelial to mesenchymal transition, cell transformation, and increased metastatic ability. Moreover, it has recently been shown that YAP plays a role in sustaining resistance to targeted therapies as well. In our work, we evaluated the role of YAP in acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in lung cancer...
November 11, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29108261/the-coiled-coil-domain-of-oncogene-rassf-7-inhibits-hippo-signaling-and-promotes-non-small-cell-lung-cancer
#9
Xiaoying Zheng, Qianze Dong, Xiupeng Zhang, Qiang Han, Xu Han, Yong Han, Jingjing Wu, Xuezhu Rong, Enhua Wang
Lung cancer is the leading cause of cancer-related deaths worldwide, and despite recent improvements in treatment patient prognosis remains dismal. In this study, we examined the role of N-terminal Ras-association domain family 7 (RASSF7) in human non-small cell lung cancer (NSCLC). We found that RASSF7 was overexpressed NSCLC tissues, which correlated with advanced TNM stage, positive lymph node metastasis, and poor prognosis. This RASSF7 overexpression promoted lung cancer cell proliferation, migration, and invasion...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29070586/fak-controls-the-mechanical-activation-of-yap-a-transcriptional-regulator-required-for-durotaxis
#10
Dariusz Lachowski, Ernesto Cortes, Benjamin Robinson, Alistair Rice, Krista Rombouts, Armando E Del Río Hernández
Focal adhesion kinase (FAK) is a key molecule in focal adhesions and regulates fundamental processes in cells such as growth, survival, and migration. FAK is one of the first molecules recruited to focal adhesions in response to external mechanical stimuli and therefore is a pivotal mediator of cell mechanosignaling, and relays these stimuli to other mechanotransducers within the cytoplasm. Yes-associated protein (YAP) has been identified recently as one of these core mechanotransducers. YAP translocates to the nucleus following changes in cell mechanics to promote the expression of genes implicated in motility, apoptosis, proliferation, and organ growth...
October 25, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29066438/polo-like-kinase-2-is-dynamically-regulated-to-coordinate-proliferation-and-early-lineage-specification-downstream-of-yes-associated-protein-1-in-cardiac-progenitor-cells
#11
Michika Mochizuki, Vera Lorenz, Robert Ivanek, Giacomo Della Verde, Emanuele Gaudiello, Anna Marsano, Otmar Pfister, Gabriela M Kuster
BACKGROUND: Recent studies suggest that adult cardiac progenitor cells (CPCs) can produce new cardiac cells. Such cell formation requires an intricate coordination of progenitor cell proliferation and commitment, but the molecular cues responsible for this regulation in CPCs are ill defined. METHODS AND RESULTS: Extracellular matrix components are important instructors of cell fate. Using laminin and fibronectin, we induced two slightly distinct CPC phenotypes differing in proliferation rate and commitment status and analyzed the early transcriptomic response to CPC adhesion (<2 hours)...
October 24, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29032615/regulation-of-the-prometastatic-neuregulin-mmp13-axis-by-src-family-kinases-therapeutic-implications
#12
Ana Orive-Ramos, Samuel Seoane, Alberto Ocaña, Atanasio Pandiella, Juan Carlos Montero
Metastatic dissemination of tumor cells is responsible for the fatal outcome of breast cancer. Therefore, understanding the mechanisms involved in dissemination is essential for the development of new therapeutic strategies to prevent metastasis. One mechanism involved in metastatic dissemination of breast cancer cells is dependent on control of the production of matrix metalloproteinases by the neuregulins (NRGs). The NRGs are polypeptide factors that act by binding to the ErbB/HER subfamily of receptor tyrosine kinases...
December 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29022919/dcz3301-a-novel-cytotoxic-agent-inhibits-proliferation-in-diffuse-large-b-cell-lymphoma-via-the-stat3-pathway
#13
Xi Sun, Bo Li, Bingqian Xie, Zhijian Xu, Gaomei Chang, Yi Tao, Yong Zhang, Shuaikang Chang, Yingcong Wang, Dandan Yu, Yongsheng Xie, Tingye Li, Houcai Wang, Gege Chen, Liangning Hu, Jun Hou, Yiwen Zhang, Wenqin Xiao, Lu Gao, Jumei Shi, Weiliang Zhu
Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma in adults, characterized by a rapidly increasing painless mass. A novel compound, DCZ3301, was synthesized that exerted direct cytotoxicity against DLBCL cell lines. The effects of DCZ3301 on DLBCL cells in vitro and in vivo and the associated mechanisms were investigated. DCZ3301 inhibited the viability of DLBCL cell lines, even in the presence of protumorigenesis cytokines. Additionally, the compound induced apoptosis and cell cycle arrest at the G2/M phase by reducing mitochondrial membrane potential...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29017756/biomechanical-strain-induced-modulation-of-proliferation-coincides-with-an-erk1-2-independent-nuclear-yap-localization
#14
Diana Hülter-Hassler, Martin Wein, Simon D Schulz, Susanne Proksch, Thorsten Steinberg, Britta A Jung, Pascal Tomakidi
Biomechanical strain induces activation of the transcriptional co-activator yes-associated protein (YAP) by nuclear re-distribution. Recent findings indicate that the mechanically responsive mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) 1/2 is involved in the amount of nuclear YAP, reflecting its activation. In this context, we conducted experiments to detect how biomechanical strain acts on the subcellular localization of YAP in periodontal cells. To this end, cells were subjected to 2...
October 7, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28982981/the-hippo-pathway-regulator-kibra-promotes-podocyte-injury-by-inhibiting-yap-signaling-and-disrupting-actin-cytoskeletal-dynamics
#15
Kristin Meliambro, Jenny S Wong, Justina Ray, Rhodora C Calizo, Sara Towne, Beatriz Cole, Fadi El Salem, Ronald E Gordon, Lewis Kaufman, John C He, Evren U Azeloglu, Kirk N Campbell
Kidney podocytes represent a key constituent of the glomerular filtration barrier. Identifying the molecular mechanisms of podocyte injury and survival is important for better understanding and management of kidney diseases. KIBRA (KIdney BRAin protein), an upstream regulator of the Hippo signaling pathway encoded by the Wwc1 gene, shares the pro-injury properties of its putative binding partner dendrin and antagonizes the pro-survival signaling of the downstream Hippo pathway effector YAP (Yes-associated protein) in Drosophila and MCF10A cells...
October 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28972170/%C3%AE-1-integrin-dependent-rac-group-i-pak-signaling-mediates-yap-activation-of-yes-associated-protein-1-yap1-via-nf2-merlin
#16
Hiba Sabra, Molly Brunner, Vinay Mandati, Bernhard Wehrle Haller, Dominique Lallemand, Anne-Sophie Ribba, Genevieve Chevalier, Philippe Guardiola, Marc R Block, Daniel Bouvard
Cell adhesion to the extracellular matrix or to surrounding cells plays a key role in cell proliferation and differentiation, and is critical for proper tissue homeostasis. An important pathway in adhesion-dependent cell proliferation is the Hippo signaling cascade, which is coregulated by the transcription factors Yes-associated protein 1 (YAP1) and transcriptional coactivator with PDZ-binding motif (TAZ). However, how cells integrate extracellular information at the molecular level to regulate YAP1 nuclear localization is still puzzling...
September 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28964793/oncogenic-determination-of-a-broad-spectrum-of-phenotypes-of-hepatocyte-derived-mouse-liver-tumors
#17
Masahiro Yamamoto, Bing Xin, Kenji Watanabe, Takako Ooshio, Kiyonaga Fujii, Xi Chen, Yoko Okada, Hiroaki Abe, Yoshimitsu Taguchi, Naoyuki Miyokawa, Hiroyuki Furukawa, Yuji Nishikawa
Activation of the phosphoinositide 3-kinase-AKT, Yes-associated protein (YAP), and MYC pathways is involved in human liver cancers, including hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). However, the nature of the interactions among these pathways has remained poorly understood. Herein, we demonstrate the coordination of these pathways during the formation of mouse liver tumors induced by hepatocyte-specific somatic integration of myristoylated AKT, mutant YAP, Myc, or their combinations. Although the introduction of YAP or Myc alone was inefficient in inducing tumors, these proteins accelerated tumorigenesis induced by AKT...
September 28, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28961951/the-polycystic-ovary-syndrome-associated-gene-yap1-is-regulated-by-gonadotropins-and-sex-steroid-hormones-in-hyperandrogenism-induced-oligo-ovulation-in-mouse
#18
Shu-Yan Ji, Xiao-Man Liu, Bo-Tai Li, Yin-Li Zhang, Hong-Bin Liu, Yu-Chao Zhang, Zi-Jiang Chen, Junping Liu, Heng-Yu Fan
STUDY QUESTION: What is the physiological function of Yes-associated protein-1 (Yap1), a susceptibility gene for polycystic ovary syndrome (PCOS), in ovarian granulosa cells (GCs)? SUMMARY ANSWER: Physiologically, steroid sex hormones stimulate follicle growth by activating YAP1; however, the preovulatory inhibition of YAP1 activity in GCs is a prerequisite of LH actions. WHAT IS KNOWN ALREADY: PCOS is a common gynecologic and endocrine disease with multiple short and long-term consequences...
October 1, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28945218/tnf%C3%AE-yap-p65-hk2-axis-mediates-breast-cancer-cell-migration
#19
Y Gao, Y Yang, F Yuan, J Huang, W Xu, B Mao, Z Yuan, W Bi
Clinical and experimental evidence indicates that macrophages could promote solid-tumor progression and metastasis. However, the mechanisms underlying this process remain unclear. Here we show that yes-associated protein 1 (YAP1), a transcriptional regulator that controls tissue growth and regeneration, has an important role in tumor necrosis factor α (TNF α)-induced breast cancer migration. Mechanistically, macrophage conditioned medium (CM) or TNFα triggers IκB kinases (IKKs)-mediated YAP phosphorylation and activation in breast cancer cells...
September 25, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28931921/an-iterative-compound-screening-contest-method-for-identifying-target-protein-inhibitors-using-the-tyrosine-protein-kinase-yes
#20
Shuntaro Chiba, Takashi Ishida, Kazuyoshi Ikeda, Masahiro Mochizuki, Reiji Teramoto, Y-H Taguchi, Mitsuo Iwadate, Hideaki Umeyama, Chandrasekaran Ramakrishnan, A Mary Thangakani, D Velmurugan, M Michael Gromiha, Tatsuya Okuno, Koya Kato, Shintaro Minami, George Chikenji, Shogo D Suzuki, Keisuke Yanagisawa, Woong-Hee Shin, Daisuke Kihara, Kazuki Z Yamamoto, Yoshitaka Moriwaki, Nobuaki Yasuo, Ryunosuke Yoshino, Sergey Zozulya, Petro Borysko, Roman Stavniichuk, Teruki Honma, Takatsugu Hirokawa, Yutaka Akiyama, Masakazu Sekijima
We propose a new iterative screening contest method to identify target protein inhibitors. After conducting a compound screening contest in 2014, we report results acquired from a contest held in 2015 in this study. Our aims were to identify target enzyme inhibitors and to benchmark a variety of computer-aided drug discovery methods under identical experimental conditions. In both contests, we employed the tyrosine-protein kinase Yes as an example target protein. Participating groups virtually screened possible inhibitors from a library containing 2...
September 20, 2017: Scientific Reports
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