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https://www.readbyqxmd.com/read/29032615/regulation-of-the-prometastatic-neuregulin-mmp13-axis-by-src-family-kinases-therapeutic-implications
#1
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...
October 15, 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
#2
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
#3
Diana Huelter-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
#4
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
#5
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
#6
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
#7
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 ovarian syndrome (PCOS), in ovarian granulosa cells? SUMMARY ANSWER: Physiologically, steroid sex hormones stimulate follicle growth by activating YAP1; however, the preovulatory inhibition of YAP1 activity in granulosa cells 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...
August 10, 2017: Molecular Human Reproduction
https://www.readbyqxmd.com/read/28945218/tnf%C3%AE-yap-p65-hk2-axis-mediates-breast-cancer-cell-migration
#8
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
#9
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
https://www.readbyqxmd.com/read/28926422/two-faces-of-hippo-activate-or-suppress-the-hippo-pathway-in-cancer
#10
Jingwen Cao, Wenlong Huang
The Hippo pathway has generated considerable interest in recent years because of its involvement in several key hallmarks of cancer progression and metastasis. Research on the Hippo signaling pathway in cancer has been used to determine the activity of yes-associated protein (YAP) in tumorigenesis and disease progression. Previous studies have shown that the Hippo pathway can be used as a target to inhibit YAP activity and is a viable treatment for cancer. However, more studies are required to further advance our understanding of the Hippo signaling pathway in cancer...
November 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28910325/src-and-fyn-dependent-apical-membrane-trafficking-events-control-endothelial-lumen-formation-during-vascular-tube-morphogenesis
#11
Dae Joong Kim, Pieter R Norden, Jocelynda Salvador, David M Barry, Stephanie L K Bowers, Ondine Cleaver, George E Davis
Here we examine the question of how endothelial cells (ECs) develop their apical membrane surface domain during lumen and tube formation. We demonstrate marked apical membrane targeting of activated Src kinases to this apical domain during early and late stages of this process. Immunostaining for phosphotyrosine or phospho-Src reveals apical membrane staining in intracellular vacuoles initially. This is then followed by vacuole to vacuole fusion events to generate an apical luminal membrane, which is similarly decorated with activated phospho-Src kinases...
2017: PloS One
https://www.readbyqxmd.com/read/28893403/energy-restriction-affect-liver-development-in-hu-sheep-ram-lambs-through-hippo-signaling-pathway
#12
Ting-Ting Zhang, Guo-Min Zhang, Yu-Hang Jin, Yi-Xuan Guo, Zhen Wang, Yi-Xuan Fan, M A El-Samahy, Feng Wang
This study aimed to evaluate the effects of dietary energy restriction on postnatal liver development in Hu sheep ram lambs. A total of 16 ram lambs were randomly divided into two groups: 100% energy requirements diet and 55% energy requirements diet, which were fed for 75 d. Results showed that the final body and liver weights decreased with energy restriction (p <0.05). Energy restriction caused a significant decrease in the levels of circulating insulin-like growth factor 1 (IGF1) and an increase in growth hormone secretion (p <0...
September 2, 2017: Tissue & Cell
https://www.readbyqxmd.com/read/28820389/hippo-pathway-brief-overview-of-its-relevance-in-cancer
#13
A L Zygulska, K Krzemieniecki, P Pierzchalski
The Hippo pathway is the major regulator of organ growth and proliferation. Described initially in Drosophila, it is now recognized as one of the most conserved molecular pathways in all metazoan. Recent studies have revealed the Hippo signalling pathway might contribute to tumorigenesis and cancer development. The core components of the Hippo pathway include the mammalian sterile 20-like kinases (MSTs), large tumour suppressor kinases (LATSs), the adaptor proteins Salvador homologue 1 (SAV1, also called WW45) and Mps One Binder kinase activator proteins...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28815883/wwc2-is-an-independent-prognostic-factor-and-prevents-invasion-via-hippo-signalling-in-hepatocellular-carcinoma
#14
Yijun Zhang, Shumei Yan, Jiewei Chen, Caixia Gan, Dong Chen, Yan Li, Jiahuai Wen, Joachim Kremerskothen, Shilu Chen, Jiangbo Zhang, Yun Cao
WWC family proteins negatively regulate HEK293 cell proliferation and organ growth by suppressing the transcriptional activity of Yes-associated protein (YAP), a major effector of the Hippo pathway. The function of the scaffolding protein WWC1 (also called KIBRA) has been intensively studied in cells and animal models. However, the expression and clinicopathologic significance of WWC2 in cancer are poorly characterized. This study aimed to clarify the biological function and mechanism of action of WWC2 in hepatocellular carcinoma (HCC)...
August 16, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28757477/the-roles-and-mechanisms-of-the-hippo-yap-signaling-pathway-in-the-nervous-system
#15
Xiao-mei Bao, Qing He, Ying Wang, Zhi-hui Huang, Zeng-qiang Yuan
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/28757470/molecular-mechanisms-of-the-mammalian-hippo-signaling-pathway
#16
Xin-yan Ji, Guoxuan Zhong, Bin Zhao
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/28724435/ww-domain-binding-protein-2-an-adaptor-protein-closely-linked-to-the-development-of-breast-cancer
#17
REVIEW
Shuai Chen, Han Wang, Yu-Fan Huang, Ming-Li Li, Jiang-Hong Cheng, Peng Hu, Chuan-Hui Lu, Ya Zhang, Na Liu, Chi-Meng Tzeng, Zhi-Ming Zhang
The WW domain is composed of 38 to 40 semi-conserved amino acids shared with structural, regulatory, and signaling proteins. WW domain-binding protein 2 (WBP2), as a binding partner of WW domain protein, interacts with several WW-domain-containing proteins, such as Yes kinase-associated protein (Yap), paired box gene 8 (Pax8), WW-domain-containing transcription regulator protein 1 (TAZ), and WW-domain-containing oxidoreductase (WWOX) through its PPxY motifs within C-terminal region, and further triggers the downstream signaling pathway in vitro and in vivo...
July 19, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28718435/agrin-to-yap-in-cancer-and-neuromuscular-junctions
#18
Wen-Cheng Xiong, Lin Mei
Agrin is utilized by motor neurons to stimulate the LRP4-MuSK receptor in muscles for neuromuscular junction (NMJ) formation. Recent studies of cancer have identified novel functions of the low-density lipoprotein receptor-related protein 4-muscle-specific kinase (LRP4-MuSK) pathway. Agrin may act as a mechanotransduction signal in the extracellular matrix (ECM) to coordinate the cross-talk between the LRP4-MuSK pathway and integrin-focal adhesion pathway. Ensuing Yes-associated protein (YAP) activation promotes hepatocellular carcinoma (HCC)...
April 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28715434/engineered-extracellular-matrices-with-controlled-mechanics-modulate-renal-proximal-tubular-cell-epithelialization
#19
Jeffrey A Beamish, Evan Chen, Andrew J Putnam
Acute kidney injury (AKI) is common and associated with significant morbidity and mortality. Recovery from many forms of AKI involves the proliferation of renal proximal tubular epithelial cells (RPTECs), but the influence of the microenvironment in which this recovery occurs remains poorly understood. Here we report the development of a poly(ethylene glycol) (PEG) hydrogel platform to study the influence of substrate mechanical properties on the proliferation of human RPTECs as a model for recovery from AKI...
2017: PloS One
https://www.readbyqxmd.com/read/28680534/nsclc-depend-upon-yap-expression-and-nuclear-localization-after-acquiring-resistance-to-egfr-inhibitors
#20
Marc McGowan, Lilach Kleinberg, Ann Rita Halvorsen, Åslaug Helland, Odd Terje Brustugun
Yes-associated protein (YAP) is a downstream target of the Hippo pathway and has been found to be oncogenic driving many cancers into developing metastatic phenotypes leading to poor survival outcomes. This study investigated if YAP expression is associated with drug resistance in two non-small cell lung cancer (NSCLC) lines (HCC827 and H1975) generated to become resistant to the EGFR tyrosine kinase inhibitors (EGFR TKI) erlotinib, gefitinib or the T790M-specific osimertinib. We found that acquired EGFR TKI resistance was associated with YAP over-expression (osimertinib-resistant cells) or YAP amplification (erlotinib- and gefitinib-resistant cells) along with EMT phenotypic changes...
March 2017: Genes & Cancer
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