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hippo pathway

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https://www.readbyqxmd.com/read/28438716/yap1-negatively-regulates-chondrocyte-differentiation-partly-by-activating-the-%C3%AE-catenin-signaling-pathway
#1
Beining Yang, Hualing Sun, Fangfang Song, Miao Yu, Yanru Wu, Jiawei Wang
YAP1 (Yes-associated protein 1) transcriptional coactivator is a downstream gene of the Hippo signaling pathway, which controls cell proliferation and differentiation. YAP1 plays a significant role in the regulation of cartilage and bone development. However, the molecular mechanism by which YAP1 regulates chondrocyte differentiation remains to be elucidated. Immunofluorescent staining was used to visualize the localization of YAP1 expression in the mouse chondroprogenitor ATDC5 cell line. ATDC5 cells with lentivirus-vector-mediated YAP1 overexpression and knockdown were established...
April 21, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28436947/dedifferentiation-into-blastomere-like-cancer-stem-cells-via-formation-of-polyploid-giant-cancer-cells
#2
N Niu, I Mercado-Uribe, J Liu
Our recent perplexing findings that polyploid giant cancer cells (PGCCs) acquired embryonic-like stemness and were capable of tumor initiation raised two important unanswered questions: how do PGCCs acquire such stemness, and to which stage of normal development do PGCCs correspond. Intriguingly, formation of giant cells due to failed mitosis/cytokinesis is common in the blastomere stage of the preimplantation embryo. However, the relationship between PGCCs and giant blastomeres has never been studied. Here, we tracked the fate of single PGCCs following paclitaxel-induced mitotic failure...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28434174/molecular-alterations-and-expression-dynamics-of-lats1-and-lats2-genes-in-non-small-cell-lung-carcinoma
#3
Showkat A Malik, Mosin S Khan, Majeed Dar, Mahboob Ul Hussain, Mohammad A Shah, Sheikh M Shafi, Syed Mudassar
Large tumor suppressor (LATS) is an important member of the Hippo pathway which can regulate organ size and cell proliferation. However, very little is known about the expression and clinical significance of LATS in lung cancer especially from this part of the world. We elucidated the frequency of LATS1 &LATS2 promoter hypermethylation (by methylation-specific PCR) and expression (by real-time PCR) in sixty nine (n = 69) Non-Small Cell Lung Cancer (NSCLC) patients and their corresponding normal lung tissue samples...
April 22, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28433598/mir-590-5p-a-density-sensitive-microrna-inhibits-tumorigenesis-by-targeting-yap1-in-colorectal-cancer
#4
Chunlin Ou, Zhenqiang Sun, Xiayu Li, Xiaoling Li, Weiguo Ren, Zailong Qin, Xuemei Zhang, Weitang Yuan, Jia Wang, Wentao Yu, Shiwen Zhang, Qiu Peng, Qun Yan, Wei Xiong, Guiyuan Li, Jian Ma
YAP1, a transcription co-activator, mediates the biological functions of the Hippo pathway. YAP1 inactivation is involved in cell-cell contact inhibition. In various tumors, YAP1 is upregulated through multiple mechanisms, and it functions as an oncogene. Here, we provided evidence that YAP1 influenced multiple signaling pathways in colorectal cancer (CRC) cells. We reported that miR-590-5p directly targets YAP1 and inhibits tumorigenesis in CRC cells both in vitro and in vivo xenograft model. We analyzed different cell densities and found that increased density caused increased expression of miR-590-5p, and decreased expression of its precursors (pri- and pre-miR-590)...
April 19, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28431572/hepatitis-c-virus-ns4b-protein-induces-epithelial-mesenchymal-transition-by-upregulation-of-snail
#5
Bicheng Hu, Shenggao Xie, Yuqian Hu, Wen Chen, Xiaofan Chen, Yi Zheng, Xinxing Wu
BACKGROUND: Chronic hepatitis C virus (HCV) infection is an important cause of hepatocellular carcinoma (HCC). Epithelial to mesenchymal transition (EMT) is a key process associated with tumor metastasis and poor prognosis. HCV infection, HCV core and NS5A protein could induce EMT process, but the role of NS4B on EMT remains poorly understood. METHODS: We overexpressed HCV NS4B protein in HepG2 cells or Huh7.5.1 cells infected by HCVcc, the E-cadherin expression, N-cadherin expression and the EMT-associated transcriptional factor Snail were determined...
April 21, 2017: Virology Journal
https://www.readbyqxmd.com/read/28430104/dissection-of-the-interaction-between-the-intrinsically-disordered-yap-protein-and-the-transcription-factor-tead
#6
Yannick Mesrouze, Fedir Bokhovchuk, Marco Meyerhofer, Patrizia Fontana, Catherine Zimmermann, Typhaine Martin, Clara Delaunay, Dirk Erdmann, Tobias Schmelzle, Patrick Chène
TEAD (TEA/ATTS domain) transcription factors are the most distal effectors of the Hippo pathway. YAP (Yes-associated protein) is a coactivator protein which, upon binding to TEAD proteins, stimulates their transcriptional activity. Since the Hippo pathway is deregulated in various cancers, designing inhibitors of the YAP:TEAD interaction is an attractive therapeutic strategy for oncology. Understanding the molecular events that take place at the YAP:TEAD interface is therefore important not only to devise drug discovery approaches, but also to gain knowledge on TEAD regulation...
April 21, 2017: ELife
https://www.readbyqxmd.com/read/28429726/verteporfin-induced-formation-of-protein-cross-linked-oligomers-and-high-molecular-weight-complexes-is-mediated-by-light-and-leads-to-cell-toxicity
#7
Eleni K Konstantinou, Shoji Notomi, Cassandra Kosmidou, Katarzyna Brodowska, Ahmad Al-Moujahed, Fotini Nicolaou, Pavlina Tsoka, Evangelos Gragoudas, Joan W Miller, Lucy H Young, Demetrios G Vavvas
Verteporfin (VP) was first used in Photodynamic therapy, where a non-thermal laser light (689 nm) in the presence of oxygen activates the drug to produce highly reactive oxygen radicals, resulting in local cell and tissue damage. However, it has also been shown that Verteporfin can have non-photoactivated effects such as interference with the YAP-TEAD complex of the HIPPO pathway, resulting in growth inhibition of several neoplasias. More recently, it was proposed that, another non-light mediated effect of VP is the formation of cross-linked oligomers and high molecular weight protein complexes (HMWC) that are hypothesized to interfere with autophagy and cell growth...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28427208/identification-of-differentially-expressed-lncrnas-involved-in-transient-regeneration-of-the-neonatal-c57bl-6j-mouse-heart-by-next-generation-high-throughput-rna-sequencing
#8
Yu-Mei Chen, Hua Li, Yi Fan, Qi-Jun Zhang, Xing Li, Li-Jie Wu, Zi-Jie Chen, Chun Zhu, Ling-Mei Qian
Previous studies have shown that mammalian cardiac tissue has a regenerative capacity. Remarkably, neonatal mice can regenerate their cardiac tissue for up to 6 days after birth, but this capacity is lost by day 7. In this study, we aimed to explore the expression pattern of long noncoding RNA (lncRNA) during this period and examine the mechanisms underlying this process. We found that 685 lncRNAs and 1833 mRNAs were differentially expressed at P1 and P7 by the next-generation high-throughput RNA sequencing...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28427193/targeting-high-aurora-kinases-expression-as-an-innovative-therapy-for-hepatocellular-carcinoma
#9
Fuchen Liu, Guangyong Wang, Xiaoqiang Wang, Zhihui Che, Wei Dong, Xinggang Guo, Zhenguang Wang, Ping Chen, Daisen Hou, Qi Zhang, Wenli Zhang, Yida Pan, Dongqin Yang, Hui Liu
The Aurora kinases A and B control tumorigenesis by inhibiting apoptosis and promoting proliferation and metastasis, however, it remains unknown whether Aurora A and B overexpressed concomitantly and its clinical significance in hepatocellular carcinoma (HCC). Here, we obsearved Aurora A and B tended to overexpress parallelly on protein level (r = 0.8679, P < 0.0001) and their co-overexpression (Aurora AHBH), associated with the worst prognosis, was an independent predictor for the survival. Importantly, with the lower IC50 and stronger anti-tumor effect than selective inhibitors, SNS-314, the pan-inhibitor of Aurora kinases, which induced YAP (Yes-associated protein) reduction and resulted in P21 accumulation, significantly promoted the polyploidy (> 4N) formation and apoptosis in HCC...
March 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28424630/hippo-pathway-and-skeletal-muscle-mass-regulation-in-mammals-a-controversial-relationship
#10
REVIEW
Olouyomi Gnimassou, Marc Francaux, Louise Deldicque
Skeletal muscle mass reflects a dynamic turnover between net protein synthesis and degradation. In addition, satellite cell inclusion may contribute to increase muscle mass while fiber loss results in a reduction of muscle mass. Since 2010, a few studies looked at the involvement of the newly discovered Hippo pathway in the regulation of muscle mass. In line with its roles in other organs, it has been hypothesized that the Hippo pathway could play a role in different regulatory mechanisms in skeletal muscle as well, namely proliferation and renewal of satellite cells, differentiation, death, and growth of myogenic cells...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28417908/cytokinesis-failure-leading-to-chromosome-instability-in-v-src-induced-oncogenesis
#11
REVIEW
Yuji Nakayama, Shuhei Soeda, Masayoshi Ikeuchi, Keiko Kakae, Naoto Yamaguchi
v-Src, an oncogene found in Rous sarcoma virus, is a constitutively active variant of c-Src. Activation of Src is observed frequently in colorectal and breast cancers, and is critical in tumor progression through multiple processes. However, in some experimental conditions, v-Src causes growth suppression and apoptosis. In this review, we highlight recent progress in our understanding of cytokinesis failure and the attenuation of the tetraploidy checkpoint in v-Src-expressing cells. v-Src induces cell cycle changes-such as the accumulation of the 4N cell population-and increases the number of binucleated cells, which is accompanied by an excess number of centrosomes...
April 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28416665/hippo-pathway-mediates-resistance-to-cytotoxic-drugs
#12
Taranjit S Gujral, Marc W Kirschner
Chemotherapy is widely used for cancer treatment, but its effectiveness is limited by drug resistance. Here, we report a mechanism by which cell density activates the Hippo pathway, which in turn inactivates YAP, leading to changes in the regulation of genes that control the intracellular concentrations of gemcitabine and several other US Food and Drug Administration (FDA)-approved oncology drugs. Hippo inactivation sensitizes a diverse panel of cell lines and human tumors to gemcitabine in 3D spheroid, mouse xenografts, and patient-derived xenograft models...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28416659/deubiquitinase-yod1-potentiates-yap-taz-activities-through-enhancing-itch-stability
#13
Youngeun Kim, Wantae Kim, Yonghee Song, Jeong-Rae Kim, Kyungjoo Cho, Hyuk Moon, Simon Weonsang Ro, Eunjeong Seo, Yeon-Mi Ryu, Seung-Jae Myung, Eek-Hoon Jho
Hippo signaling controls the expression of genes regulating cell proliferation and survival and organ size. The regulation of core components in the Hippo pathway by phosphorylation has been extensively investigated, but the roles of ubiquitination-deubiquitination processes are largely unknown. To identify deubiquitinase(s) that regulates Hippo signaling, we performed unbiased siRNA screening and found that YOD1 controls biological responses mediated by YAP/TAZ. Mechanistically, YOD1 deubiquitinates ITCH, an E3 ligase of LATS, and enhances the stability of ITCH, which leads to reduced levels of LATS and a subsequent increase in the YAP/TAZ level...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28415761/yap-promotes-tumorigenesis-and-cisplatin-resistance-in-neuroblastoma
#14
Chao Yang, Juan Tan, Jun Zhu, Shan Wang, Guanghui Wei
The transcriptional co-activator Yes-associated protein (YAP) is essential for Hippo pathway-driven tumorigenesis in various cancers. However, the expression and function of YAP in neuroblastoma remains elusive. Here, we show that YAP was highly expressed in Neuroblastoma (NB) and expression levels correlated with advanced tumor staging. Knockdown of YAP significantly impaired neuroblastoma proliferation, tumorigenesis, and invasion in vitro. Injection of the YAP inhibitor, Peptide 17, dramatically prevented neuroblastoma subcutaneous tumor growth by efficiently downregulating YAP expression in tumors...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415606/taz-induces-lung-cancer-stem-cell-properties-and-tumorigenesis-by-up-regulating-aldh1a1
#15
Jihang Yu, Adel Alharbi, Hongchao Shan, Yawei Hao, Brooke Snetsinger, Michael J Rauh, Xiaolong Yang
Recent studies suggest that lung cancer stem cells (CSCs) may play major roles in lung cancer. Therefore, identification of lung CSC drivers may provide promising targets for lung cancer. TAZ is a transcriptional co-activator and key downstream effector of the Hippo pathway, which plays critical roles in various biological processes. TAZ has been shown to be overexpressed in lung cancer and involved in tumorigenicity of lung epithelial cells. However, whether TAZ is a driver for lung CSCs and tumor formation in vivo is unknown...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28413159/the-hippo-pathway-maintains-the-equatorial-division-plane-in-the-ciliate-tetrahymena
#16
Yu-Yang Jiang, Wolfgang Maier, Ralf Baumeister, Gregory Minevich, Ewa Joachimiak, Zheng Ruan, Natarajan Kannan, Diamond Clarke, Joseph Frankel, Jacek Gaertig
The mechanisms that govern pattern formation within the cell are poorly understood. Ciliates carry on their surface an elaborate pattern of cortical organelles that are arranged along the anteroposterior and circumferential axes by largely unknown mechanisms. Ciliates divide by tandem duplication: the cortex of the pre-division cell is remodeled into two similarly-sized and complete daughters. In the conditional cdaI-1 mutant of Tetrahymena thermophile, the division plane migrates from its initially correct equatorial position toward the cell's anterior, resulting in unequal cell division, and defects in nuclear divisions and cytokinesis...
April 16, 2017: Genetics
https://www.readbyqxmd.com/read/28412244/a-central-role-for-cadherin-signaling-in-cancer
#17
REVIEW
Antonis Kourtidis, Ruifeng Lu, Lindy J Pence, Panos Z Anastasiadis
Cadherins are homophilic adhesion molecules with important functions in cell-cell adhesion, tissue morphogenesis, and cancer. In epithelial cells, E-cadherin accumulates at areas of cell-cell contact, coalesces into macromolecular complexes to form the adherens junctions (AJs), and associates via accessory partners with a subcortical ring of actin to form the apical zonula adherens (ZA). As a master regulator of the epithelial phenotype, E-cadherin is essential for the overall maintenance and homeostasis of polarized epithelial monolayers...
April 12, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28408625/ets-dependent-transcriptional-upregulation-of-the-transcriptional-co-activator-taz-promotes-cell-migration-and-metastasis-in-prostate-cancer
#18
Chen-Ying Liu, Tong Yu, Yuji Huang, Long Cui, Wanjin Hong
Prostate cancer is a very common malignant disease and a leading cause of death for men in the western world. Tumorigenesis and progression of prostate cancer involves multiple signaling pathways, including Hippo pathway. Yes-associated protein (YAP) is the downstream transcriptional co-activator of Hippo pathway, is overexpressed in the prostate cancer, and plays a vital role in the tumorigenesis and cancer progression of prostate cancer. However, the role of the YAP paralog and another downstream effector of Hippo pathway, transcriptional co-activator with PDZ-binding motif (TAZ), in prostate cancer has not been fully elucidated...
April 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28402144/expression-and-localization-of-yap-and-taz-during-development-of-the-mandibular-first-molar-in-rats
#19
B Zhang, B Y Sun, Y W Ji, Y P Zhang, X X Wang, X Xu, Y Wen
Yes-associated protein (Yap) and transcriptional coactivator with PDZ-binding motif (Taz) are two downstream factors in the Hippo signaling pathway. Yap and Taz participate in regulating organ size, stem cell self-renewal, proliferation and differentiation. We investigated the spatial-temporal expression and relative expression levels of Yap and Taz using immunohistochemistry and real-time polymerase chain reaction. We found Yap and Taz in the oral epithelium and mesenchyme at embryonic (E) day 14.5 (E14.5) and E16...
2017: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/28401020/control-of-tissue-size-and-development-by-a-regulatory-element-in-the-yorkie-3-utr
#20
Takanari Umegawachi, Hideki Yoshida, Hiromu Koshida, Momoko Yamada, Yasuyuki Ohkawa, Tetsuya Sato, Mikita Suyama, Henry M Krause, Masamitsu Yamaguchi
Regulation of the Hippo pathway via phosphorylation of Yorkie (Yki), the Drosophila homolog of human Yes-associated protein 1, is conserved from Drosophila to humans. Overexpression of a non-phosphorylatable form of Yki induces severe overgrowth in adult fly eyes. Here, we show that yki mRNA associates with microsomal fractions and forms foci that partially colocalize to processing bodies in the vicinity of endoplasmic reticulum. This localization is dependent on a stem-loop (SL) structure in the 3' untranslated region of yki...
2017: American Journal of Cancer Research
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