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Hippo signalling

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https://www.readbyqxmd.com/read/29049318/short-chain-fatty-acid-receptors-inhibit-invasive-phenotypes-in-breast-cancer-cells
#1
Madhumathi Thirunavukkarasan, Chao Wang, Angad Rao, Tatsuma Hind, Yuan Ru Teo, Abrar Al-Mahmood Siddiquee, Mohamed Ally Ibrahim Goghari, Alan Prem Kumar, Deron R Herr
Short chain fatty acids (2 to 6 carbons in length) are ubiquitous lipids that are present in human plasma at micromolar concentrations. In addition to serving as metabolic precursors for lipid and carbohydrate synthesis, they also act as cognate ligands for two known G protein-coupled receptors (GPCRs), FFAR2 and FFAR3. While there is evidence that these receptors may inhibit the progression of colorectal cancer, their roles in breast cancer cells are largely unknown. We evaluated the effects of enforced overexpression of these receptors in two phenotypically distinct breast cancer cell lines: MCF7 and MDA-MD-231...
2017: PloS One
https://www.readbyqxmd.com/read/29046731/promoter-methylation-inhibits-expression-of-tumor-suppressor-kibra-in-human-clear-cell-renal-cell-carcinoma
#2
Katrin Schelleckes, Boris Schmitz, Giuliano Ciarimboli, Malte Lenders, Hermann J Pavenstädt, Edwin Herrmann, Stefan-Martin Brand, Eva Brand
BACKGROUND: KIBRA has been suggested as a key regulator of the Hippo signaling pathway, regulating organ size, cell contact inhibition, tissue regeneration as well as tumorigenesis and cystogenesis. We recently reported that human KIBRA expression depends on a complex alternative CpG-rich promoter system. Our current study aimed at the identification of epigenetic mechanisms associated with alterations in KIBRA expression regulation. RESULTS: We identified two separated methylation-sensitive CpG islands located to independent KIBRA promoter regions...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29045821/mir-93-5p-promotes-gastric-cancer-cell-progression-via-inactivation-of-the-hippo-signaling-pathway
#3
Li Li, Jun Deng, Shanshan Huang, Yi Wang, Lingling Zhu, Yuan Cao, Jianping Xiong
MiR-93-5p has been previously found to be associated with gastric cancer (GC) tumorigenesis; however, the current understanding of its function in this context remains largely incomplete. In the present study, we showed that miR-93-5p was upregulated in GC tissues. We also demonstrated that miR-93-5p overexpression promoted the proliferation, migration, invasion, and chemoresistance of SGC-7901 cells in vitro, and conversely, that endogenously silencing miR-93-5p expression induced the opposite effects in HGC-27 cells...
October 15, 2017: Gene
https://www.readbyqxmd.com/read/29039607/downregulation-of-mir-874-3p-promotes-chemotherapeutic-resistance-in-colorectal-cancer-via-inactivation-of-the-hippo-signaling-pathway
#4
Kaiqian Que, Yuanhe Tong, Ganbo Que, Li Li, Hongcheng Lin, Shuai Huang, Ruoyu Wang, Langlang Tang
Overcoming resistance to chemotherapy is an arduous challenge in the treatment of colorectal cancer (CRC), particularly since the underlying molecular mechanisms remain obscure. In the present study, we reported that miR‑874-3p was markedly downregulated in CRC tissues compared with that in adjacent normal colorectal epithelial tissues. Upregulation of miR-874-3p attenuated the chemoresistance of CRC cells to 5-fluorouracil (5-FU) in vitro and in vivo. Conversely, inhibition of miR-874-3p yielded an opposite effect...
October 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29039486/analysis-of-mirna-expression-profiling-in-human-umbilical-vein-endothelial-cells-affected-by-heat-stress
#5
Jie Liu, Guoguo Zhu, Siya Xu, Shixin Liu, Qiping Lu, Zhongzhi Tang
To investigate the regulation of endothelial cell (EC) microRNAs (miRNAs) altered by heat stress, miRNA microarrays and bioinformatics methods were used to determine changes in miRNA profiles and the pathophysiological characteristics of differentially expressed miRNAs. A total of 31 differentially expressed miRNAs were identified, including 20 downregulated and 11 upregulated miRNAs. Gene Ontology (GO) enrichment analysis revealed that the validated targets of the differentially expressed miRNAs were significantly enriched in gene transcription regulation...
October 5, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29018616/integration-of-lncrna-mirna-mrna-reveals-novel-insights-into-oviposition-regulation-in-honey-bees
#6
Xiao Chen, Ce Ma, Chao Chen, Qian Lu, Wei Shi, Zhiguang Liu, Huihua Wang, Haikun Guo
BACKGROUND: The honey bee (Apis mellifera) is a highly diverse species commonly used for honey production and pollination services. The oviposition of the honey bee queen affects the development and overall performance of the colony. To investigate the ovary activation and oviposition processes on a molecular level, a genome-wide analysis of lncRNAs, miRNAs and mRNA expression in the ovaries of the queens was performed to screen for differentially expressed coding and noncoding RNAs. Further analysis identified relevant candidate genes or RNAs...
2017: PeerJ
https://www.readbyqxmd.com/read/28990064/gaseous-signalling-molecule-so2-via-hippo%C3%A2-mst-pathway-to-improve-myocardial-fibrosis-of-diabetic-rats
#7
Maojun Liu, Shengquan Liu, Wenting Tan, Fen Tang, Junrong Long, Zining Li, Biao Liang, Chun Chu, Jun Yang
Recent studies have indicated the existence of an endogenous sulfur dioxide (SO2)‑generating system in the cardiovascular system. The present study aimed to discuss the function and regulatory mechanism of gaseous signal molecule SO2 in inhibiting apoptosis and endoplasmic reticulum stress (ERS) via the Hippo‑MST signaling pathway to improve myocardial fibrosis of diabetic rats. A total of 40 male Sprague‑Dawley rats were randomly divided into four groups (10 rats per group): Normal control group (control group), diabetic rats group [streptozotocin (STZ) group], SO2 intervention group (STZ+SO2 group) and diabetes mellitus rats treated with L‑Aspartic acid β‑hydroxamate (HDX) group (HDX group)...
October 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28984872/p53-shades-of-hippo
#8
Noa Furth, Yael Aylon, Moshe Oren
The three p53 family members, p53, p63 and p73, are structurally similar and share many biochemical activities. Yet, along with their common fundamental role in protecting genomic fidelity, each has acquired distinct functions related to diverse cell autonomous and non-autonomous processes. Similar to the p53 family, the Hippo signaling pathway impacts a multitude of cellular processes, spanning from cell cycle and metabolism to development and tumor suppression. The core Hippo module consists of the tumor-suppressive MST-LATS kinases and oncogenic transcriptional co-effectors YAP and TAZ...
October 6, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28982981/the-hippo-pathway-regulator-kibra-promotes-podocyte-injury-by-inhibiting-yap-signaling-and-disrupting-actin-cytoskeletal-dynamics
#9
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/28982536/hoxa1-targets-signaling-pathways-during-neural-differentiation-of-es-cells-and-mouse-embryogenesis
#10
Bony De Kumar, Hugo J Parker, Ariel Paulson, Mark E Parrish, Julia Zeitlinger, Robb Krumlauf
Hoxa1 has important functional roles in neural crest specification, hindbrain patterning and heart and ear development, yet the enhancers and genes that are targeted by Hoxa1 are largely unknown. In this study, we performed a comprehensive analysis of Hoxa1 target genes using genome-wide Hoxa1 binding data in mouse ES cells differentiated with retinoic acid (RA) into neural fates in combination with differential gene expression analysis in Hoxa1 gain- and loss-of-function mouse and zebrafish embryos. Our analyses reveal that Hoxa1-bound regions show epigenetic marks of enhancers, occupancy of Hox cofactors and differential expression of nearby genes, suggesting that these regions are enriched for enhancers...
October 2, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28979669/comprehensive-analysis-of-long-non-coding-rna-pvt1-gene-interaction-regulatory-network-in-hepatocellular-carcinoma-using-gene-microarray-and-bioinformatics
#11
Yu Zhang, Yi-Wu Dang, Xiao Wang, Xia Yang, Rui Zhang, Zi-Li Lv, Gang Chen
PVT1 has been reported to be involved in the tumorigenesis and development of different cancers. However, the role of PVT1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we applied gene microarray analysis to detect differentially expressed genes (DEGs) between PVT1 RNAi groups and controls. We initially investigated and confirmed PVT1 expression in HCC using The Cancer Genome Atlas (TCGA). The potential genes and pathways associated with PVT1 were also analyzed. We also performed bioinformatics analyses (Gene Ontology (GO), pathway, Kyoto Encyclopedia of Genes and Genomes (KEGG), and network analyses) to explore the underlying pathways and networks of these potential genes...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28973878/yap-taz-cdc42-signaling-regulates-vascular-tip-cell-migration
#12
Masahide Sakabe, Jieqing Fan, Yoshinobu Odaka, Ning Liu, Aishlin Hassan, Xin Duan, Paige Stump, Luke Byerly, Megan Donaldson, Jiukuan Hao, Marcus Fruttiger, Qing Richard Lu, Yi Zheng, Richard A Lang, Mei Xin
Angiogenesis and vascular remodeling are essential for the establishment of vascular networks during organogenesis. Here we show that the Hippo signaling pathway effectors YAP and TAZ are required, in a gene dosage-dependent manner, for the proliferation and migration of vascular endothelial cells (ECs) during retinal angiogenesis. Intriguingly, nuclear translocation of YAP and TAZ induced by Lats1/2-deletion blocked endothelial migration and phenocopied Yap/Taz-deficient mutants. Furthermore, overexpression of a cytoplasmic form of YAP (YAPS127D) partially rescued the migration defects caused by loss of YAP and TAZ function...
September 25, 2017: Proceedings of the National Academy of Sciences of the United States of America
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
#13
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/28969054/usp21-regulates-hippo-pathway-activity-by-mediating-mark-protein-turnover
#14
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...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28969031/down-regulation-of-lincrna-p21-contributes-to-gastric-cancer-development-through-hippo-independent-activation-of-yap
#15
Ying Chen, Guoqing Wei, Hongwei Xia, Huangfei Yu, Qiuling Tang, Feng Bi
Long intergenic non-coding RNA p21 (lincRNA-p21), known as the direct transcriptional target of p53, was found down-regulated in several human solid tumors. However, little is known about the role of lincRNA-p21 in gastric cancer. The expression levels of lincRNA-p21 in tissue samples and cell lines were detected by qRT-PCR. MGC-803 and MKN-45 cells were transfected with siRNAs targeting lincRNA-p21 or control siRNAs to determine the effect of reduced lincRNA-p21 expression on tumorigenesis. We also overexpressed lincRNA-p21 in MGC-803 cells...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28968962/protein-salvador-homolog-1-acts-as-a-tumor-suppressor-and-is-modulated-by-hypermethylation-in-pancreatic-ductal-adenocarcinoma
#16
Lei Wang, Mei Wang, Chenxi Hu, Pengping Li, Yun Qiao, Youyou Xia, Liang Liu, Xiaodong Jiang
Salvador (SAV) is a gene product that contains two protein-protein interaction modules known as WW domains and is believed to act as a scaffolding protein for Hippo and Warts. SAV1 is the human homolog of Salvador, which is the most well characterized upstream signaling component of Hippo pathway. Although its role in some tumors is known, SAV1 function in other types of tumors, including pancreatic tumor, is still obscure. Here, we determined the role of SAV1 in pancreatic ductal adenocarcinoma (PDAC) development and progression...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28966941/increased-expression-of-the-tight-junction-protein-tjp1-zo-1-is-associated-with-upregulation-of-taz-tead-activity-and-an-adult-tissue-stem-cell-signature-in-carfilzomib-resistant-multiple-myeloma-cells-and-high-risk-multiple-myeloma-patients
#17
Irene Riz, Robert G Hawley
Tight junction protein 1 (TJP1) has recently been proposed as a biomarker to identify multiple myeloma (MM) patients most likely to respond to bortezomib- and carfilzomib-based proteasome inhibitor regimens. Herein we report increased expression of TJP1 during the adaptive response mediating carfilzomib resistance in the LP-1/Cfz MM cell line. Moreover, increased TJP1 expression delineated a subset of relapsed/refractory MM patients on bortezomib-based therapy sharing an LP-1/Cfz-like phenotype characterized by activation of interacting transcriptional effectors of the Hippo signaling cascade (TAZ and TEAD1) and an adult tissue stem cell signature...
July 2017: Oncoscience
https://www.readbyqxmd.com/read/28964625/regulation-of-the-hippo-pathway-transcription-factor-tead
#18
REVIEW
Kimberly C Lin, Hyun Woo Park, Kun-Liang Guan
The TEAD transcription factor family is best known for transcriptional output of the Hippo signaling pathway and has been implicated in processes such as development, cell growth and proliferation, tissue homeostasis, and regeneration. Our understanding of the functional importance of TEADs has increased dramatically since its initial discovery three decades ago. The majority of our knowledge of TEADs is in the context of Hippo signaling as nuclear DNA-binding proteins passively activated by Yes-associated protein (YAP) and transcriptional activator with PDZ-binding domain (TAZ), transcription coactivators downstream of the Hippo pathway...
September 27, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28963395/lncrna-wires-up-hippo-and-hedgehog-signaling-to-reprogramme-glucose-metabolism
#19
Xin Zheng, Han Han, Guang-Ping Liu, Yan-Xiu Ma, Ruo-Lang Pan, Ling-Jie Sang, Rui-Hua Li, Luo-Jia Yang, Jeffrey R Marks, Wenqi Wang, Aifu Lin
The Hippo pathway plays essential roles in organ size control and cancer prevention via restricting its downstream effector, Yes-associated protein (YAP). Previous studies have revealed an oncogenic function of YAP in reprogramming glucose metabolism, while the underlying mechanism remains to be fully clarified. Accumulating evidence suggests long noncoding RNAs (lncRNAs) as attractive therapeutic targets, given their roles in modulating various cancer-related signaling pathways. In this study, we report that lncRNA breast cancer anti-estrogen resistance 4 (BCAR4) is required for YAP-dependent glycolysis...
September 28, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28962630/%C3%AE-catenin-mediated-yap-signaling-promotes-human-glioma-growth
#20
Yan Wang, Peng Pan, Zhaohao Wang, Yu Zhang, Peng Xie, Decheng Geng, Yang Jiang, Rutong Yu, Xiuping Zhou
BACKGROUND: Hippo/YAP pathway is known to be important for development, growth and organogenesis, and dysregulation of this pathway leads to tumor progression.We and others find that YAP is up-regulated in human gliomas and associated with worse prognosis of patients. However, the role and mechanism of YAP in glioma progression is largely unknown. METHODS: The expression of YAP in glioma tissues was detected by quantitative polymerase chain reaction (qPCR) and immunoblotting...
September 29, 2017: Journal of Experimental & Clinical Cancer Research: CR
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