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https://www.readbyqxmd.com/read/29416763/dysregulation-of-yap-by-the-hippo-pathway-is-involved-in-intervertebral-disc-degeneration-cell-contact-inhibition-and-cell-senescence
#1
Cong Zhang, Feng Wang, Zhiyang Xie, Lu Chen, Arjun Sinkemani, Haomin Yu, Kun Wang, Lu Mao, Xiaotao Wu
The Hippo pathway plays important roles in wound healing, tissue repair and regeneration, and in the treatment of degenerative diseases, by regulating cell proliferation and apoptosis in mammals. Intervertebral disc degeneration (IDD) is one of the major causes of low back pain, a widespread issue associated with a heavy economic burden. However, the mechanism underlying how the Hippo pathway regulates IDD is not well understood. Here, we demonstrate that the Hippo pathway is involved in natural IDD. Activation and dephosphorylation of yes-associated protein (YAP) were observed in younger rat discs, and decreased gradually with age...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29403552/downregulation-of-yap-inhibits-proliferation-and-induces-apoptosis-in-eca-109-cells
#2
Mu Cui, Zhen Li
A previous study reported that Yes-associated protein (YAP) gene was overexpressed in esophageal squamous cell carcinoma (ESCC); however, the exact role of YAP in ESCC remains largely unclear. The present study aimed to investigate the effects of YAP inhibition on ESCC. In order to investigate the exact role of YAP in ESCC cells, a stable YAP low-expression ESCC cell line was established using YAP-small interfering RNA. MTT assay was performed to examine the cell proliferation ability, while flow cytometry were used to detect the cell apoptosis and cell cycle distribution...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29400695/claudin-18-mediated-yap-activity-regulates-lung-stem-and-progenitor-cell-homeostasis-and-tumorigenesis
#3
Beiyun Zhou, Per Flodby, Jiao Luo, Dan R Castillo, Yixin Liu, Fa-Xing Yu, Alicia McConnell, Bino Varghese, Guanglei Li, Nyam-Osor Chimge, Mitsuhiro Sunohara, Michael N Koss, Wafaa Elatre, Peter Conti, Janice M Liebler, Chenchen Yang, Crystal N Marconett, Ite A Laird-Offringa, Parviz Minoo, Kunliang Guan, Barry R Stripp, Edward D Crandall, Zea Borok
Claudins, the integral tight junction (TJ) proteins that regulate paracellular permeability and cell polarity, are frequently dysregulated in cancer; however, their role in neoplastic progression is unclear. Here, we demonstrated that knockout of Cldn18, a claudin family member highly expressed in lung alveolar epithelium, leads to lung enlargement, parenchymal expansion, increased abundance and proliferation of known distal lung progenitors, the alveolar epithelial type II (AT2) cells, activation of Yes-associated protein (YAP), increased organ size, and tumorigenesis in mice...
February 5, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29366445/clinical-implications-of-the-hippo-yap-pathway-in-multiple-cancer-contexts
#4
Han-Byul Kim, Seung-Jae Myung
The Hippo pathway plays prominent and widespread roles in various forms of human carcinogenesis. Specifically, the Yes-associated protein (YAP), a downstream effector of the Hippo pathway, can lead to excessive cell proliferation and the inhibition of apoptosis, resulting in tumorigenesis. It was reported that the YAP is strongly elevated in multiple types of human malignancies such as breast, lung, small intestine, colon, and liver cancers. Recent work indicates that, surprisingly, Hippo signaling components' (SAV1, MST1/2, Lats1/2) mutations are virtually absent in human cancer, rendering this signaling an unlikely candidate to explain the vigorous activation of the YAP in most, if not all human tumors and an activated YAP promotes the resistance to RAF-, MAPK/ERK Kinase (MEK)-, and Epidermal growth factor receptor (EGFR)-targeted inhibitor therapy...
January 25, 2018: BMB Reports
https://www.readbyqxmd.com/read/29344656/liraglutide-suppresses-proliferation-and-induces-adipogenic-differentiation-of-3t3-l1-cells-via-the-hippo-yap-signaling-pathway
#5
Yongmei Li, Jianying Du, Endong Zhu, Juanjuan Zhang, Jie Han, Wei Zhao, Bei Sun, Derun Tian
Liraglutide, as a glucagon-like peptide‑1 analogue, is used to treat type 2 diabetes mellitus and obesity. Previous findings have demonstrated the effects of liraglutide on adipogenesis; however, the underlying mechanism involved in this process remains to be elucidated. In the present study, to certify the effect of liraglutide on adipogenesis and explore the possible underlying mechanism involved in this process, preadipocyte 3T3‑L1 cells were cultured in adipocyte‑inducing medium and treated with liraglutide...
January 16, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29321482/enhanced-yap-expression-leads-to-egfr-tki-resistance-in-lung-adenocarcinomas
#6
Ting-Fang Lee, Yu-Chi Tseng, Phung Anh Nguyen, Yu-Chuan Li, Chao-Chi Ho, Cheng-Wen Wu
Epidermal growth factor receptor (EGFR) mutation is prevalently expressed in lung adenocarcinoma cases and acts as one of the major driving oncogenes. EGFR tyrosine kinase inhibitors (TKIs) have been used in patients with EGFR-mutant as an effective targeted therapy in lung adenocarcinoma, but drug resistance and tumor recurrence inevitably occurs. Recently, Yes-associate protein (YAP) has been reported to promote multiple cancer cell properties, such as promoting cell proliferation, epithelial-mesenchymal transition and drug resistance...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29316729/wnt-rspo-and-hippo-signalling-in-the-intestine-and-intestinal-stem-cells
#7
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/29228123/role-of-yes-associated-protein-1-angiomotin-and-mitogen-activated-kinase-kinase-1-2-in-development-of-the-bovine-blastocyst
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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