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Notch-Wnt crosstalk

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https://www.readbyqxmd.com/read/28645563/bruceine-d-inhibits-hepatocellular-carcinoma-growth-by-targeting-%C3%AE-catenin-jagged1-pathways
#1
Ziying Cheng, Xing Yuan, Yi Qu, Xia Li, Guozhen Wu, Chenwei Li, Xianpeng Zu, Niao Yang, Xisong Ke, Juan Zhou, Ning Xie, Xike Xu, Shanrong Liu, Yunheng Shen, Huiliang Li, Weidong Zhang
Hepatocellular carcinoma (HCC) is known for high mortality and limited available treatments. Aberrant activation of the Wnt and Notch signaling pathways is critical to liver carcinogenesis and progression. Here, we identified a small molecule, bruceine D (BD), as a Notch inhibitor, using an RBP-Jκ-dependent luciferase-reporter system. BD significantly inhibited liver tumor growth and enhanced the therapeutic effects of sorafenib in various murine HCC models. Mechanistically, BD promotes proteasomal degradation of β-catenin and the depletion of its nuclear accumulation, which in turn disrupts the Wnt/β-catenin-dependent transcription of the Notch ligand Jagged1 in HCC...
June 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28562343/the-role-of-notch-signaling-in-gastric-carcinoma-molecular-pathogenesis-and-novel-therapeutic-targets
#2
REVIEW
Yizheng Yao, Ying Ni, Jiawen Zhang, Hua Wang, Shihe Shao
Notch signaling, an evolutionarily conserved signaling cascade system, is involved in promoting the progression of different types of cancers. Within the past decades, the Notch signaling pathway has increasingly been shown to have a primary role in deciding the fate of cancer cells and cancer stem cells in the stomach. Most components of Notch signaling are strongly expressed at different levels in gastric carcinoma tissue samples and are associated with a considerable number of clinical parameters. Moreover, crosstalk signaling between the Notch pathway and the Wnt, Ras, and NF-κB pathways promotes the process of gastric carcinogenesis...
May 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28501774/tuning-of-major-signaling-networks-tgf-%C3%AE-wnt-notch-and-hedgehog-by-mirnas-in-human-stem-cells-commitment-to-different-lineages-possible-clinical-application
#3
REVIEW
Sedigheh Fekri Aval, Hajie Lotfi, Roghayeh Sheervalilou, Nosratollah Zarghami
Two distinguishing characteristics of stem cells, their continuous division in the undifferentiated state and growth into any cell types, are orchestrated by a number of cell signaling pathways. These pathways act as a niche factor in controlling variety of stem cells. The core stem cell signaling pathways include Wingless-type (Wnt), Hedgehog (HH), and Notch. Additionally, they critically regulate the self-renewal and survival of cancer stem cells. Conversely, stem cells' main properties, lineage commitment and stemness, are tightly controlled by epigenetic mechanisms such as DNA methylation, histone modifications and non-coding RNA-mediated regulatory events...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28245235/the-role-of-the-hes1-crosstalk-hub-in-notch-wnt-interactions-of-the-intestinal-crypt
#4
Sophie K Kay, Heather A Harrington, Sarah Shepherd, Keith Brennan, Trevor Dale, James M Osborne, David J Gavaghan, Helen M Byrne
The Notch pathway plays a vital role in determining whether cells in the intestinal epithelium adopt a secretory or an absorptive phenotype. Cell fate specification is coordinated via Notch's interaction with the canonical Wnt pathway. Here, we propose a new mathematical model of the Notch and Wnt pathways, in which the Hes1 promoter acts as a hub for pathway crosstalk. Computational simulations of the model can assist in understanding how healthy intestinal tissue is maintained, and predict the likely consequences of biochemical knockouts upon cell fate selection processes...
February 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28186678/gamma-secretase-inhibitor-ix-gsi-impairs-concomitant-activation-of-notch-and-wnt-beta-catenin-pathways-in-cd44-gastric-cancer-stem-cells
#5
Samarpita Barat, Xi Chen, Khac Cuong Bui, Przemyslaw Bozko, Julian Götze, Matthias Christgen, Till Krech, Nisar P Malek, Ruben R Plentz
Cancer stem cells (CSC) are associated with tumor resistance and are characterized in gastric cancer (GC). Studies have indicated that Notch and wnt-beta-catenin pathways are crucial for CSC development. Using CD44(+) CSCs, we investigated the role of these pathways in GC carcinogenesis. We performed cell proliferation, wound healing, invasion, tumorsphere, and apoptosis assays. Immunoblot analysis of downstream signaling targets of Notch and wnt-beta-catenin were tested after gamma-secretase inhibitor IX (GSI) treatment...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27633988/notch-wnt-bmp-crosstalk-regulates-radial-patterning-in-the-mouse-cochlea-in-a-spatiotemporal-manner
#6
Vidhya Munnamalai, Donna M Fekete
The sensory cells of the mammalian organ of Corti assume a precise mosaic arrangement during embryonic development. Manipulation of Wnt signaling can modulate the proliferation of cochlear progenitors, but whether Wnts are responsible for patterning compartments, or specific hair cells within them, is unclear. To address how the precise timing of Wnt signaling impacts patterning across the radial axis, mouse cochlear cultures were initiated at embryonic day 12.5 and subjected to pharmacological treatments at different stages...
November 1, 2016: Development
https://www.readbyqxmd.com/read/27590724/wnt-signalling-pathways-and-micrornas-network-in-carcinogenesis-experimental-and-bioinformatics-approaches
#7
REVIEW
Emenike K Onyido, Eloise Sweeney, Abdolrahman Shams Nateri
Over the past few years, microRNAs (miRNAs) have not only emerged as integral regulators of gene expression at the post-transcriptional level but also respond to signalling molecules to affect cell function(s). miRNAs crosstalk with a variety of the key cellular signalling networks such as Wnt, transforming growth factor-β and Notch, control stem cell activity in maintaining tissue homeostasis, while if dysregulated contributes to the initiation and progression of cancer. Herein, we overview the molecular mechanism(s) underlying the crosstalk between Wnt-signalling components (canonical and non-canonical) and miRNAs, as well as changes in the miRNA/Wnt-signalling components observed in the different forms of cancer...
September 2, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27580895/preliminary-analysis-of-micrornas-expression-profiling-in-mc3t3-e1-cells-exposed-to-fluoride
#8
Yan Wang, Xiuyun Zhang, Zhitao Zhao, Hui Xu
Overexposure to fluoride from environmental sources can cause serious public health problems. Disrupted osteoblast function and impaired bone formation were found to be associated with excessive fluoride exposure. A massive analysis of microRNAs (miRNAs) was used to figure out the possible pathways in which fluoride affects osteoblast function. MC3T3-E1 cells were treated with 8 mg/L of fluorine for 7 days. Total RNA of cells was extracted, and their integrity and purity were tested. RNA samples were analyzed by using miRNA array, including miRNA labeling, hybridization, scanning, and expression data analysis to compare the profiling of miRNA expression between control and fluoride-treated group...
April 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/27563484/tgf-%C3%AE-and-bmp-signaling-in-osteoblast-skeletal-development-and-bone-formation-homeostasis-and-disease
#9
REVIEW
Mengrui Wu, Guiqian Chen, Yi-Ping Li
Transforming growth factor-beta (TGF-β) and bone morphogenic protein (BMP) signaling has fundamental roles in both embryonic skeletal development and postnatal bone homeostasis. TGF-βs and BMPs, acting on a tetrameric receptor complex, transduce signals to both the canonical Smad-dependent signaling pathway (that is, TGF-β/BMP ligands, receptors, and Smads) and the non-canonical-Smad-independent signaling pathway (that is, p38 mitogen-activated protein kinase/p38 MAPK) to regulate mesenchymal stem cell differentiation during skeletal development, bone formation and bone homeostasis...
2016: Bone Research
https://www.readbyqxmd.com/read/27443002/-the-expressions-of-the-notch-and-wnt-signaling-pathways-and-their-significance-in-the-repair-process-of-alveolar-bone-defects-in-rabbits-with-bone-marrow-stem-cells-compounded-with-platelet-rich-fibrin
#10
Chunmei Zhou, Shuhui Li, Naikuli Wenqiguli, Li Yu, Lu Zhao, Peiling Wu, Tuerxun Nijiati
OBJECTIVE: We explored the expressions of the Notch and Wnt signaling pathways and their significance in the repair process of alveolar bone defects by establishing animal models with a composite of autologous bone marrow mesenchymal stem cells (BMSCs) and platelet-rich fibrin (PRF) to repair bone defects in the extraction sockets of rabbits. METHODS: A total of 36 two-month-old male New Zealand white rabbits were randomly divided into four groups, and the left mandibular incisors of all the rabbits were subjected to minimally invasive removalunder general anesthesia...
April 2016: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/27435629/co-regulation-of-the-notch-and-wnt-signaling-pathways-promotes-supporting-cell-proliferation-and-hair-cell-regeneration-in-mouse-utricles
#11
Jingfang Wu, Wenyan Li, Chen Lin, Yan Chen, Cheng Cheng, Shan Sun, Mingliang Tang, Renjie Chai, Huawei Li
This work sought to determine the crosstalk between the Notch and Wnt signaling pathways in regulating supporting cell (SC) proliferation and hair cell (HC) regeneration in mouse utricles. We cultured postnatal day (P)3 and P60 mouse utricles, damaged the HCs with gentamicin, and treated the utricles with the γ-secretase inhibitor DAPT to inhibit the Notch pathway and with the Wnt agonist QS11 to active the Wnt pathway. We also used Sox2-CreER, Notch1-flox (exon 1), and Catnb-flox (exon 3) transgenic mice to knock out the Notch pathway and activate the Wnt pathway in Sox2+ SCs...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27220406/notch-signaling-represses-hypoxia-inducible-factor-1%C3%AE-induced-activation-of-wnt-%C3%AE-catenin-signaling-in-osteoblasts-under-cobalt-mimicked-hypoxia
#12
Chen-Tian Li, Jian-Xiu Liu, Bo Yu, Rui Liu, Chao Dong, Song-Jian Li
The modification of Wnt and Notch signaling pathways by hypoxia, and its association with osteoblast proliferation and apoptosis remain to be fully elucidated. To investigate Wnt-Notch crosstalk, and its role in hypoxia-induced osteoblast proliferation and apoptosis regulation, the present study investigated the effects of cobalt‑mimicked hypoxia on the mouse pre-osteoblast-like cell line, MC3T3‑E1, when the Notch signals were repressed using a γ‑secretase inhibitor DAPT. The data showed that the cobalt‑mimicked hypoxia suppressed cell proliferation under normal conditions, but increased cell proliferation under conditions of Notch repression, in a concentration‑dependent manner...
July 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27066918/hes1-in-immunity-and-cancer
#13
Aradhana Rani, Roseanna Greenlaw, Richard A Smith, Christine Galustian
Hairy and enhancer of split homolog-1 (HES1) is a part of an extensive family of basic helix-loop-helix (bHLH) proteins and plays a crucial role in the control and regulation of cell cycle, proliferation, cell differentiation, survival and apoptosis in neuronal, endocrine, T-lymphocyte progenitors as well as various cancers. HES1 is a transcription factor which is regulated by the NOTCH, Hedgehog and Wnt signalling pathways. Aberrant expression of these pathways is a common feature of cancerous cells. There appears to be a fine and complicated crosstalk at the molecular level between the various signalling pathways and HES1, which contributes to its effects on the immune response and cancers such as leukaemia...
August 2016: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/26872974/regulation-of-monocarboxylic-acid-transporter-1-trafficking-by-the-canonical-wnt-%C3%AE-catenin-pathway-in-rat-brain-endothelial-cells-requires-cross-talk-with-notch-signaling
#14
Zejian Liu, Mary Sneve, Thomas A Haroldson, Jeffrey P Smith, Lester R Drewes
The transport of monocarboxylate fuels such as lactate, pyruvate, and ketone bodies across brain endothelial cells is mediated by monocarboxylic acid transporter 1 (MCT1). Although the canonical Wnt/β-catenin pathway is required for rodent blood-brain barrier development and for the expression of associated nutrient transporters, the role of this pathway in the regulation of brain endothelial MCT1 is unknown. Here we report expression of nine members of the frizzled receptor family by the RBE4 rat brain endothelial cell line...
April 8, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/26592459/the-notch-intracellular-domain-integrates-signals-from-wnt-hedgehog-tgf%C3%AE-bmp-and-hypoxia-pathways
#15
REVIEW
Tilman Borggrefe, Matthias Lauth, An Zwijsen, Danny Huylebroeck, Franz Oswald, Benedetto Daniele Giaimo
Notch signaling is a highly conserved signal transduction pathway that regulates stem cell maintenance and differentiation in several organ systems. Upon activation, the Notch receptor is proteolytically processed, its intracellular domain (NICD) translocates into the nucleus and activates expression of target genes. Output, strength and duration of the signal are tightly regulated by post-translational modifications. Here we review the intracellular post-translational regulation of Notch that fine-tunes the outcome of the Notch response...
February 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/26206577/morphogen-related-therapeutic-targets-for-liver-fibrosis
#16
REVIEW
Eileen Fung, Hidekazu Tsukamoto
Recent research on hepatic stellate cells (HSCs) has spotlighted the involvement of morphogens in their cell fate determination in liver fibrosis. Temporally and spatially expressed during embryonic development, morphogens are involved in regulation of cell proliferation and differentiation, and tissue patterning. In normal adult liver, morphogens are generally expressed at low levels. However, in liver disease, myofibroblastic HSCs express morphogens such as Wnt, Shh, Necdin, DLK1, and Notch as part of their participation in fibrogenesis and wound healing...
September 2015: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/26106366/crosstalk-of-the-insulin-like-growth-factor-receptor-with-the-wnt-signaling-pathway-in-breast-cancer
#17
REVIEW
Lauren M Rota, Teresa L Wood
The insulin-like growth factor system has long been considered a pathway that promotes cell proliferation, survival, and transformation, and is thus a promoter of tumorigenesis. However, recent failure of clinical trials for IGF-1R inhibitors reveals the need for a better understanding of how this pathway functions in specific tumor subtypes. Ongoing studies are designed to uncover biomarkers and downstream targets to enhance therapeutic strategies. Other approaches in specific tumor models reveal complex interactions between IGF signaling and other tumor initiating pathways...
2015: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/25965442/molecular-signalling-in-hepatocellular-carcinoma-role-of-and-crosstalk-among-wnt-%C3%A3-catenin-sonic-hedgehog-notch-and-dickkopf-1
#18
REVIEW
Alex Giakoustidis, Dimitrios Giakoustidis, Satvinder Mudan, Argyrios Sklavos, Roger Williams
Hepatocellular carcinoma is the sixth most common cancer worldwide. In the majority of cases, there is evidence of existing chronic liver disease from a variety of causes including viral hepatitis B and C, alcoholic liver disease and nonalcoholic steatohepatitis. Identification of the signalling pathways used by hepatocellular carcinoma cells to proliferate, invade or metastasize is of paramount importance in the discovery and implementation of successfully targeted therapies. Activation of Wnt/β-catenin, Notch and Hedgehog pathways play a critical role in regulating liver cell proliferation during development and in controlling crucial functions of the adult liver in the initiation and progression of human cancers...
May 2015: Canadian Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/25866502/modelling-coupled-oscillations-in-the-notch-wnt-and-fgf-signaling-pathways-during-somitogenesis-a-comprehensive-mathematical-model
#19
Hong-yan Wang, Yan-xin Huang, Li-hua Zheng, Yong-li Bao, Lu-guo Sun, Yin Wu, Chun-lei Yu, Zhen-bo Song, Ying Sun, Guan-nan Wang, Zhi-qiang Ma, Yu-xin Li
Somite formation in the early stage of vertebrate embryonic development is controlled by a complicated gene network named segmentation clock, which is defined by the periodic expression of genes related to the Notch, Wnt, and the fibroblast growth factor (FGF) pathways. Although in recent years some findings about crosstalk among the Notch, Wnt, and FGF pathways in somitogenesis have been reported, the investigation of their crosstalk mechanisms from a systematic point of view is still lacking. In this study, a more comprehensive mathematical model was proposed to simulate the dynamics of the Notch, Wnt, and FGF pathways in the segmentation clock...
2015: Computational Intelligence and Neuroscience
https://www.readbyqxmd.com/read/25850553/targeting-notch-hedgehog-and-wnt-pathways-in-cancer-stem-cells-clinical-update
#20
REVIEW
Naoko Takebe, Lucio Miele, Pamela Jo Harris, Woondong Jeong, Hideaki Bando, Michael Kahn, Sherry X Yang, S Percy Ivy
During the past decade, cancer stem cells (CSCs) have been increasingly identified in many malignancies. Although the origin and plasticity of these cells remain controversial, tumour heterogeneity and the presence of small populations of cells with stem-like characteristics is established in most malignancies. CSCs display many features of embryonic or tissue stem cells, and typically demonstrate persistent activation of one or more highly conserved signal transduction pathways involved in development and tissue homeostasis, including the Notch, Hedgehog (HH), and Wnt pathways...
August 2015: Nature Reviews. Clinical Oncology
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