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hippo pathway

Binyi Lin, Tianchi Chen, Qijun Zhang, Xiaoxiao Lu, Zhiyun Zheng, Jun Ding, Jinfeng Liu, Zhe Yang, Lei Geng, Liming Wu, Lin Zhou, Shusen Zheng
To investigate the potential oncogene promoting recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT), throughput RNA sequencing was performed in a subgroup of HCC patients. The up-regulated FAM83D in HCC tissues was found and further verified in 150 patients by real-time PCR and immunohistochemistry. FAM83D overexpression significantly correlated with high HCC recurrence rate following LT and poor HCC characteristics such as high AFP, poor differentiation. Of cancer stem cells (CSCs) markers, CD44 expression was effectively suppressed when FAM83D was knocked down by siRNA...
October 18, 2016: Oncotarget
Junyong Zhang, Zuojin Liu, Zhengrong Lian, Rui Liao, Yi Chen, Yi Qin, Jinlong Wang, Qing Jiang, Xiaobo Wang, Jianping Gong
Monoacylglycerol lipase (MAGL) is a key enzyme in lipid metabolism that is demonstrated to be involved in tumor progression through both energy supply of fatty acid (FA) oxidation and enhancing cancer cell malignance. The aim of this study was to investigate whether MAGL could be a potential therapeutic target and prognostic indicator for hepatocellular carcinoma (HCC). To evaluate the relationship between MAGL levels and clinical characteristics, a tissue microarray (TMA) of 353 human HCC samples was performed...
October 21, 2016: Scientific Reports
Kwong-Fai Wong, Angela M Liu, Wanjin Hong, Zhi Xu, John M Luk
The Hippo pathway regulates the down-stream target Yes-associated protein (YAP) to maintain organ homeostasis, which is commonly inactivated in many types of cancers. However, how cell adhesion dysregulates the Hippo pathway activating YAP oncogene in hepatocellular carcinoma (HCC) remains unclear. Our findings demonstrate that α2β1 integrin (but not other β1 integrins) expressed in HCC cells, after binding to collagen extracellular matrix, could inhibit MST1 kinase phosphorylation and activate YAP pro-oncogenic activities...
October 19, 2016: Oncotarget
Yue Wang, Runping Fang, Ming Cui, Weiying Zhang, Xiao Bai, Huawei Wang, Bowen Liu, Xiaodong Zhang, Lihong Ye
The oncoprotein Yes-associated protein (YAP) in Hippo pathway plays crucial roles in the development of cancer. However, the mechanism of YAP regulation in cancer remains poorly understood. Here, we supposed that the oncoprotein hepatitis B X-interacting protein (HBXIP) might be involved in the modulation of YAP in liver cancer. Interestingly, our data showed that the expression levels of HBXIP were positively associated with those of YAP in clinical hepatocellular carcinoma (HCC) samples by immunohistochemistry (IHC) staining and real-time PCR assays...
October 17, 2016: Cancer Letters
Weijie Li, Shicai Dong, Wei Wei, Guangxiu Wang, Anling Zhang, Peiyu Pu, Zhifan Jia
The transcriptional coactivator with PDZ-binding motif (TAZ) is one of the important downstream effectors of Hippo pathway. In this study, the potential implication of TAZ in gliomagenesis was explored. TAZ expression was identified to be upregulated in glioma specimens and positively correlated with tumor grade. Meanwhile, its expression in nucleus was increased more significantly with the ascending order of tumor grade. Knocking down TAZ inhibited glioma cell proliferation, invasion and promoted apoptosis...
October 13, 2016: Oncotarget
Marie-Julie Nokin, Florence Durieux, Paul Peixoto, Barbara Chiavarina, Olivier Peulen, Arnaud Blomme, Andrei Turtoi, Brunella Costanza, Nicolas Smargiasso, Dominique Baiwir, Jean L Scheijen, Casper G Schalkwijk, Justine Leenders, Pascal De Tullio, Elettra Bianchi, Marc Thiry, Koji Uchida, David A Spiegel, James R Cochrane, Craig A Hutton, Edwin De Pauw, Philippe Delvenne, Dominique Belpomme, Vincent Castronovo, Akeila Bellahcène
Metabolic reprogramming toward aerobic glycolysis unavoidably induces methylglyoxal (MG) formation in cancer cells. MG mediates the glycation of proteins to form advanced glycation end products (AGEs). We have recently demonstrated that MG-induced AGEs are a common feature of breast cancer. Little is known regarding the impact of MG-mediated carbonyl stress on tumor progression. Breast tumors with MG stress presented with high nuclear YAP, a key transcriptional co-activator regulating tumor growth and invasion...
October 19, 2016: ELife
Clara Ugolini, Nicla Borrelli, Cristina Niccoli, Rossella Elisei, David Viola, Paolo Vitti, Paolo Miccoli, Fulvio Basolo
CONTEXT: Yes-associated protein-1 (YAP-1) is a player of the Hippo pathway and is involved in regulating cell proliferation. YAP-1 is overexpressed in papillary and anaplastic thyroid cancers. However, a correlation between YAP-1 expression and outcome in thyroid carcinoma has not been conclusively demonstrated. OBJECTIVE: This study was designed to clarify whether YAP-1 may be considered a marker of worse prognosis and outcome in thyroid cancer. DESIGN: A large series of cases of thyroid cancer with a long follow-up were investigated for YAP-1 expression...
October 7, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
Jyoti R Misra, Kenneth D Irvine
The protocadherins Dachsous and Fat initiate a signaling pathway that controls growth and planar cell polarity by regulating the membrane localization of the atypical myosin Dachs. How Dachs is regulated by Fat signaling has remained unclear. Here we identify the vamana gene as playing a crucial role in regulating membrane localization of Dachs and in linking Fat and Dachsous to Dachs regulation. Vamana, an SH3-domain-containing protein, physically associates with and co-localizes with Dachs and promotes its membrane localization...
October 7, 2016: Developmental Cell
Raimundo Barbosa-Barros, Andrés Ricardo Pérez-Riera, Luiz Carlos de Abreu, Ricardo Paulo de Sousa-Rocha, Danielli Oliveira da Costa Lino, Adrian Baranchuk, Li Zhang
Left ventricular involvement in the advanced stage of arrhythmogenic cardiomyopathy (AC) is an evolution of this desmosomopathy. Mutation in intercalated discs explains the phenotypic variability. Abnormal trafficking of the intercalated discs at the site of end-to-end contacts between cardiomyocytes and the canonical Wnt/β-catenin and Hippo signaling pathways have been implicated. In AC, T-wave inversion in lateral leads is the hallmark of left ventricular (LV) involvement. We herein report a case of isolated LV AC in which the initial ECG has typical features: fragmented QRS (fQRS), Twave inversion (TWI) in lateral leads, and ventricular tachycardia from inferobasal LV wall...
September 8, 2016: Journal of Electrocardiology
Huabo Wang, Jie Lu, Lia R Edmunds, Sucheta Kulkarni, James Dolezal, Junyan Tao, Sarangarajan Ranganathan, Laura Jackson, Marc Fromherz, Donna Beer Stolz, Radha Uppala, Sivakama Bharathi, Satdarshan P Monga, Eric S Goetzman, Edward V Prochownik
Hepatoblastoma (HB) is associated with aberrant activation of the β-catenin and Hippo/YAP signaling pathways. Over-expression of mutant β-catenin and YAP in mice induces HBs that express high levels of c-Myc (Myc). In light of recent observations that Myc in unnecessary for long-term hepatocyte proliferation, we have now examined its role in HB pathogenesis using the above model. While Myc was found to be dispensable for in vivo HB initiation it was necessary to sustain rapid tumor growth. Gene expression profiling identified key molecular differences between myc+/+ (WT) and myc-/- (KO) hepatocytes and HBs that explain these behaviors...
October 13, 2016: Journal of Biological Chemistry
Maurizio Pesce, Elisa Messina, Isotta Chimenti, Antonio Paolo Beltrami
The life-long story of the heart starts concomitantly with primary differentiation events occurring in multipotent progenitors located in the so called heart tube. This initially tubular structure starts a looping process which leads to formation of the final four chambered heart with a primary contribution of geometric and position-associated cell sensing. While this establishes the correct patterning of the final cardiac structure, it also feedbacks to fundamental cellular machineries controlling proliferation and differentiation, thus ensuring a coordinated restriction of cell growth and a myocyte terminal differentiation...
October 13, 2016: Stem Cells and Development
Takaaki Higashi, Hiromitsu Hayashi, Yuki Kitano, Kensuke Yamamura, Takayoshi Kaida, Kota Arima, Katsunobu Taki, Shigeki Nakagawa, Hirohisa Okabe, Hidetoshi Nitta, Katsunori Imai, Daisuke Hashimoto, Akira Chikamoto, Toru Beppu, Hideo Baba
Diabetes and obesity are associated with non-alcoholic steatohepatitis and an increased incidence of hepatocellular carcinoma (HCC). TAZ and YAP are equivalently placed downstream effectors of the Hippo pathway with oncogenic roles in human cancers. Statins are commonly used to patients with metabolic problems as hypercholesterolemia. Statins also have anti-cancer properties, and the cross-talk between mevalonate pathway and Hippo pathway was known. The aim of this study is to confirm the statin's anti-cancer effects on HCC cells and its survival benefits in HCC patients with curative surgery...
November 2016: Medical Oncology
Hao Zhang, Decheng Geng, Jian Gao, Yanhua Qi, Yi Shi, Yan Wang, Yang Jiang, Yu Zhang, Jiale Fu, Yu Dong, Shangfeng Gao, Rutong Yu, Xiuping Zhou
Dysregulation of Hippo/YAP signaling leads to aberrant cell growth and neoplasia. Although the roles and regulation of Hippo/YAP signaling were extensively studied in cancer biology recently, study systematically checking the expression pattern of core components of this pathway at the tumor tissue level remains lacking. In this study, we thoroughly examined the profile of core components of Hippo/YAP signaling in patient specimens both at the mRNA and at protein levels. We found that the mRNA level of YAP1/TAZ and their target genes, CRY61, CTGF, and BIRC5, was remarkably amplified in glioma tissues...
October 7, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Ruyi Zou, Da Li, Gang Wang, Mo Zhang, Yili Zhao, Zeyu Yang
The transcriptional coactivator with PDZ-binding motif (TAZ) functions as a downstream regulatory target in the Hippo signaling pathway that plays various roles. We previously developed a cell-based assay and identified the TAZ activator IBS008738 as a potential therapeutic target for glucocorticoid-induced atrophy. To further explore the application of IBS008738 in various muscle-related diseases, we examined the function of IBS008738 in inflammatory cytokine-mediated mouse muscle responses after traumatic brain injury (TBI)...
October 7, 2016: Inflammation
Anna Di Benedetto, Marcella Mottolese, Francesca Sperati, Cristiana Ercolani, Luigi Di Lauro, Laura Pizzuti, Patrizia Vici, Irene Terrenato, Abeer M Shaaban, Sreekumar Sundara-Rajan, Matthew P Humphries, Maddalena Barba, Valerie Speirs, Ruggero De Maria, Marcello Maugeri-Saccà
Male breast cancer (MBC) is a rare hormone-driven disease often associated with obesity. HMG-CoAR is the central enzyme of the mevalonate pathway, a molecular route deputed to produce cholesterol and steroid-based hormones. HMG-CoAR regulates the oncogenic Hippo transducers TAZ/YAP whose expression was previously associated with shorter survival in MBC. 225 MBC samples were immunostained for HMG-CoAR and 124 were considered eligible for exploring its relationship with hormone receptors (ER, PgR, AR), Hippo transducers and survival outcomes...
October 7, 2016: Scientific Reports
Ying-Bei Chen, Jianing Xu, Anders Jacobsen Skanderup, Yiyu Dong, A Rose Brannon, Lu Wang, Helen H Won, Patricia I Wang, Gouri J Nanjangud, Achim A Jungbluth, Wei Li, Virginia Ojeda, A Ari Hakimi, Martin H Voss, Nikolaus Schultz, Robert J Motzer, Paul Russo, Emily H Cheng, Filippo G Giancotti, William Lee, Michael F Berger, Satish K Tickoo, Victor E Reuter, James J Hsieh
Renal cell carcinomas with unclassified histology (uRCC) constitute a significant portion of aggressive non-clear cell renal cell carcinomas that have no standard therapy. The oncogenic drivers in these tumours are unknown. Here we perform a molecular analysis of 62 high-grade primary uRCC, incorporating targeted cancer gene sequencing, RNA sequencing, single-nucleotide polymorphism array, fluorescence in situ hybridization, immunohistochemistry and cell-based assays. We identify recurrent somatic mutations in 29 genes, including NF2 (18%), SETD2 (18%), BAP1 (13%), KMT2C (10%) and MTOR (8%)...
October 7, 2016: Nature Communications
Rafael H Abduch, Ana Carolina Bueno, Leticia F Leal, Marcelo M Cavalcanti, Débora C Gomes, Silvia R Brandalise, Maria J Masterallo, José A Yunes, Carlos E Martinelli, Luiz G Tone, Silvio Tucci, Carlos A F Molina, Fernando S Ramalho, Ayrton C Moreira, Izilda A Cardinalli, Carlos A Scrideli, Leandra N Z Ramalho, Margaret de Castro, Sonir R Antonini
BACKGROUND: Overexpression of the oncogene yes-associated-protein-1 (YAP1) is associated with increased cell proliferation in human cancers. YAP1 is a potential target of the Wnt/beta-catenin pathway, which plays an important role in adrenocortical tumors (ACT). The role of YAP1 in adrenocortical tumorigenesis has not been assessed. AIMS: To evaluate YAP1 expression in normal adrenals and pediatric ACT and its association with disease outcome. To investigate the interaction between YAP1 and the Wnt/beta-catenin pathway in adrenocortical cells...
October 1, 2016: Oncotarget
Ramazan Abylkassov, Yingqiu Xie
Yes-associated protein (YAP) is an oncoprotein located in the cytoplasm in an inactive form, and when activated, it translocates to the nucleus and activates the transcription of genes responsible for cell division and apoptosis. YAP is one of the downstream regulatory proteins in the Hippo signaling pathway, which is important in cell proliferation and regeneration. Due to its great importance, YAP is regulated very strictly by different regulatory systems. The present review will focus on the canonical pathways of YAP, and will provide details on the most recent findings regarding its regulation and role in tumorigenesis, specifically in prostate tumor progression...
October 2016: Oncology Letters
A Sebio, S Stintzing, V Heinemann, Y Sunakawa, W Zhang, W Ichikawa, A Tsuji, T Takahashi, A Parek, D Yang, S Cao, Y Ning, S Stremitzer, S Matsusaka, S Okazaki, A Barzi, M D Berger, H-J Lenz
The Hippo pathway is involved in colorectal cancer (CRC) development and progression. The Hippo regulator Rassf1a is also involved in the Ras signaling cascade. In this work, we tested single nucleotide polymorphisms within Hippo components and their association with outcome in CRC patients treated with cetuximab. Two cohorts treated with cetuximab plus chemotherapy were evaluated (198 RAS wild-type (WT) patients treated with first-line FOLFIRI plus Cetuximab within the FIRE-3 trial and 67 Ras WT patients treated either with first-line mFOLFOX6 or SOX plus Cetuximab)...
October 4, 2016: Pharmacogenomics Journal
Murugavel Ponnusamy, Pei-Feng Li, Kun Wang
Cardiomyocyte proliferation and regeneration are key to the functional recovery of myocardial tissue from injury. In the recent years, studies on cardiomyocyte proliferation overturned the traditional belief that adult cardiomyocytes permanently withdraw from the cell cycle activity. Hence, targeting cardiomyocyte proliferation is one of the potential therapeutic strategies for myocardial regeneration and repair. To achieve this, a deep understanding of the fundamental mechanisms involved in cardiomyocyte cell cycle as well as differences between neonatal and adult cardiomyocytes' cell cycle activity is required...
September 30, 2016: Cellular and Molecular Life Sciences: CMLS
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