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https://www.readbyqxmd.com/read/28822004/in-vitro-validation-of-the-hippo-pathway-as-a-pharmacological-target-for-canine-mammary-gland-tumors
#1
Samantha Guillemette, Charlène Rico, Philippe Godin, Derek Boerboom, Marilène Paquet
Canine mammary tumors (CMTs) are the most common neoplasms in intact female dogs. Some clinical and molecular similarities between certain CMT subtypes and breast cancer make them a potential model for the study of the human disease. As misregulated Hippo signaling is thought to play an important role in breast cancer development and also occurs in CMTs, we sought to determine if Hippo represents a valid pharmacological target for the treatment of CMTs. Six CMT cell lines were assessed for their expression of the Hippo pathway effectors YAP and TAZ and for their sensitivity to verteporfin, an inhibitor of YAP-mediated transcriptional coactivation...
August 18, 2017: Journal of Mammary Gland Biology and Neoplasia
https://www.readbyqxmd.com/read/28820389/hippo-pathway-brief-overview-of-its-relevance-in-cancer
#2
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
#3
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/28809862/gnaq-and-gna11-mutations-and-downstream-yap-activation-in-choroidal-nevi
#4
M J C Vader, M C Madigan, M Versluis, H M Suleiman, G Gezgin, N A Gruis, J J Out-Luiting, W Bergman, R M Verdijk, M J Jager, P A van der Velden
BACKGROUND: Mutations in GNAQ/11 genes are considered an early event in the development of uveal melanoma that may derive from a pre-existing nevus. The Hippo pathway, by way of YAP activation, rather than MAP kinase, has a role in the oncogenic capacity of GNAQ/11 mutations. METHODS: We investigated 16 nevi from 13 human eyes for driver GNAQ/11 mutations using droplet digital PCR and determined whether nevi are clonal by quantifying mutant nevus cell fractions...
August 15, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28805663/yap-taz-regulates-sprouting-angiogenesis-and-vascular-barrier-maturation
#5
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/28804541/a-potential-role-for-the-hippo-pathway-protein-yap-in-controlling-proliferation-cell-cycle-progression-and-autophagy-in-bcpap-and-ki-thyroid-papillary-carcinoma-cells
#6
Zeming Liu, Wen Zeng, Shi Wang, Xiangwang Zhao, Yawen Guo, Pan Yu, Xingjie Yin, Chunping Liu, Tao Huang
PURPOSE: The aims were two-fold: first, to examine the expression of Yes-activated protein (YAP), a key Hippo pathway regulator, in clinical thyroid papillary carcinoma samples and to correlate this with clinicopathological parameters; second, to explore the role of YAP in regulating cell growth and division in vitro. METHODS AND RESULTS: YAP expression was determined by immunohistochemistry of clinical thyroid papillary carcinoma tissue microarrays and expression was correlated with clinicopathological parameters...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28795673/-under-expression-of-lats1-promotes-the-differentiation-proliferation-and-migration-of-mesenchymal-stem-cells-by-inhibition-the-hippo-signaling-pathway-in-vitro
#7
Lang Li, Liang Dong, Jiaojie Hui, Fei Gao, Qiuhui Wang, Lan Yang, Jiangqian Zhang, Jie Yan
OBJECTIVE: To explore the effects of under-expression of large tumor suppressor 1 (LATS1) on activation of Hippo signaling pathway and differentiation, proliferation, migration of bone marrow mesenchymal stem cells (mMSCs) of mice in vitro. METHODS: mMSCs of C57BL/6 mice were divided into normal control (MSC) group, empty vector control (MSC-GFP) group, LATS1-over-expressing (MSC-LATS1) group, empty vector without LATS1 shRNA control (MSC-shControl) group and LATS1-under-expressing (MSC-shLATS1) group...
August 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28775168/jcad-promotes-progression-of-non-alcoholic-steatohepatitis-to-liver-cancer-by-inhibiting-lats2-kinase-activity
#8
Juan Ye, Tian Sheng Li, Gang Xu, Yi-Ming Zhao, Ning-Ping Zhang, Jia Fan, Jian Wu
Non-alcoholic steatohepatitis-associated hepatocellular carcinoma (NASH-HCC) is a malignancy whose incidents is rapidly increasing. However, the mechanisms that drive development of HCC in a steatotic microenvironment remain unknown. Here we report that the obesity-associated protein JCAD is expressed at significantly higher levels in human NASH-HCC specimens compared to peri-carcinoma specimens. High JCAD expression was verified in multiple hepatoma cell lines. Forced overexpression of JCAD in hepatoma cells promoted tumor growth and proliferation; whereas JCAD silencing yielded opposite effects...
August 3, 2017: Cancer Research
https://www.readbyqxmd.com/read/28767425/usp21-regulates-hippo-pathway-activity-by-mediating-mark-protein-turnover
#9
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/28761168/yap-activates-the-hippo-pathway-in-a-negative-feedback-loop
#10
Xiaoming Dai, Huan Liu, Shuying Shen, Xiaocan Guo, Huan Yan, Xinyan Ji, Li Li, Jun Huang, Xin-Hua Feng, Bin Zhao
No abstract text is available yet for this article.
August 2017: Cell Research
https://www.readbyqxmd.com/read/28759011/phosphorylated-mtor-and-yap-serve-as-prognostic-markers-and-therapeutic-targets-in-gliomas
#11
Mei Liu, Yong Lin, Xian-Chao Zhang, Yu-Huan Tan, Yue-Liang Yao, Juan Tan, Xia Zhang, You-Hong Cui, Xindong Liu, Yan Wang, Xiu-Wu Bian
Glioma is the most prevalent type of tumor in the brain and is comprised of grades I-IV, according to the WHO classification system. Grade IV glioma is also known as glioblastoma multiforme (GBM), the most malignant type of glioma. Glioma is characterized by a complex molecular background, and gene profiling studies have disclosed critical genetic events in human gliomas, which make targeted therapies the most promising therapeutic strategy. However, crosstalk between the targeted signaling pathways may hinder the efficacy of targeted therapies in gliomas...
July 31, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28757481/the-roles-of-yap-t425a-mutation-in-the-regulation-of-yap-activity
#12
Yang Yanglu, Zou Zhuangzhi, Fang Yuan, Mao Beibei
The Hippo signaling pathway plays a critical role in body development and tissue growth. As the core effector of the Hippo signaling pathway, Yes-associated protein (YAP) has been reported to be involved in various kinds of human cancers. However, the mechanism for the regulation of YAP activity has not been completely understood. In this study, we constructed a YAP Thr425Ala mutant and found that this mutation decreased YAP transcriptional activity. Further, T425A retained YAP in the cytoplasm without affecting the phosphorylation of YAP S127...
July 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28757479/the-functions-of-the-hippo-signaling-pathway-in-immune-cells
#13
Yu Shujuan, Geng Jing, Chen Lanfen
The Hippo signaling pathway, first identified in Drosophila, has emerged as a critical regulator for controlling the size of organs. Activation of the Hippo signaling pathway negatively regulates the Yorkie ortholog YAP in multiple organs, important in the regulation of cell proliferation, differentiation, and apoptosis during development. The Serine/Threonine protein kinases MST1 and MST2, mammalian homologs of the Drosophila Hippo kinase, play central roles in the Hippo signaling pathway in mammals. Recent studies reveal that non-canonical Hippo signaling pathways are also involved in the regulation of various other biological processes, particularly the important roles of MST1 and MST2 kinases in immune cell activation, adhesion, migration, growth, and apoptosis...
July 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28757477/the-roles-and-mechanisms-of-the-hippo-yap-signaling-pathway-in-the-nervous-system
#14
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
#15
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
#16
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
#17
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/28754671/src-inhibits-the-hippo-tumor-suppressor-pathway-through-tyrosine-phosphorylation-of-lats1
#18
Yuan Si, Xinyan Ji, Xiaolei Cao, Xiaoming Dai, Lingyi Xu, Hongxia Zhao, Xiaocan Guo, Huan Yan, Haitao Zhang, Chu Zhu, Qi Zhou, Mei Tang, Zongping Xia, Li Li, Yu-Sheng Cong, Sheng Ye, Ting-Bo Liang, Xin-Hua Feng, Bin Zhao
The Hippo pathway regulates cell proliferation, apoptosis and stem cell self-renewal and its inactivation in animal models causes organ enlargement followed by tumorigenesis. Hippo pathway deregulation occurs in many human cancers but the underlying mechanisms are not fully understood. Here we report tyrosine phosphorylation of the Hippo pathway tumor suppressor LATS1 as a mechanism underlying its regulation by cell adhesion. A tyrosine kinase library screen identified Src as the kinase to directly phosphorylate LATS1 on multiple residues, causing attenuated Mob kinase activator binding and structural alteration of the substrate-binding pocket in the kinase domain...
July 28, 2017: Cancer Research
https://www.readbyqxmd.com/read/28752853/regulation-of-hippo-pathway-transcription-factor-tead-by-p38-mapk-induced-cytoplasmic-translocation
#19
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/28745315/mir-302-367-lats2-yap-pathway-is-essential-for-prostate-tumor-propagating-cells-and-promotes-the-development-of-castration-resistance
#20
Y Guo, J Cui, Z Ji, C Cheng, K Zhang, C Zhang, M Chu, Q Zhao, Z Yu, Y Zhang, Y-X Fang, W-Q Gao, H H Zhu
Clinical intervention for patients with advanced prostate cancer (PCa) remains challenging due to the inevitable recurrence of castration-resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT). Cancer stem cells (CSCs) with serial tumor-propagating capacity are considered to be the driving force for PCa progression and recurrence. In this study, we report that the miR-302/367 cluster, a previously identified potent pluripotency regulator, is upregulated in prostate tumors. Specifically, the forced expression of the miR-302/367 cluster accelerates the in vitro and in vivo growth of PCa cells and their resistance to androgen ablation, whereas the knockdown of the miR-302/367 cluster using anti-sense RNA suppresses the incidence of formation, growth rate and endpoint weight of PCa cell tumors...
July 24, 2017: Oncogene
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