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Notch pathway

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https://www.readbyqxmd.com/read/29029162/aberrant-global-and-jagged-mediated-notch-signaling-disrupts-segregation-between-wt1-expressing-and-steroidogenic-tissues-in-zebrafish
#1
Chih-Wei Chou, Jamie Lin, Yun-Jin Jiang, Yi-Wen Liu
Though the zebrafish interrenal tissue has been used as a model for steroidogenesis and genesis of the adrenal gland, its specification and morphogenesis is still largely unclear. In this study, we explored how the WT1-expressing cells are segregated from the SF-1-expressing steroidogenic cells in the zebrafish model. The interrenal tissue precursors expressing ff1b, the equivalent of mammalian SF-1, are derived from wt1-expressing pronephric primordia in the zebrafish embryo. Through histochemistry and in situ hybridization, we demonstrated that the size of functionally-differentiated interrenal tissue was significantly increased upon a global inhibition of the Notch signaling pathway, which was accompanied by a disrupted segregation between the wt1- and ff1b-expressing cells...
September 29, 2017: Endocrinology
https://www.readbyqxmd.com/read/29027990/il6-blockade-potentiates-the-anti-tumor-effects-of-%C3%AE-secretase-inhibitors-in-notch3-expressing-breast-cancer
#2
Dong Wang, Jiahui Xu, Bingjie Liu, Xueyan He, Lei Zhou, Xin Hu, Feng Qiao, Anli Zhang, Xiaojun Xu, Huafeng Zhang, Max S Wicha, Lixing Zhang, Zhi-Ming Shao, Suling Liu
Notch pathways have important roles in carcinogenesis including pathways involving the Notch1 and Notch2 oncogenes. Pan-Notch inhibitors, such as gamma secretase inhibitors (GSIs), have been used in the clinical trials, but the outcomes of these trials have been insufficient and have yielded unclear. In the present study, we demonstrated that GSIs, such as MK-0752 and RO4929097, inhibit breast tumor growth, but increase the breast cancer stem cell (BCSC) population in Notch3-expressing breast cancer cells, in a process that is coupled with IL6 induction and is blocked by the IL6R antagonist Tocilizumab (TCZ)...
October 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29024000/myeloid-notch1-deficiency-activates-rhoa-rock-pathway-and-aggravates-hepatocellular-damage-in-mouse-ischemic-livers
#3
Ling Lu, Shi Yue, Longfeng Jiang, Changyong Li, Qiang Zhu, Michael Ke, Hao Lu, Xuehao Wang, Ronald W Busuttil, Qi-Long Ying, Jerzy W Kupiec-Weglinski, Bibo Ke
Notch signaling plays an emerging role in the regulation of immune cell development and function during inflammatory response. Activation of the ras homolog gene family, member A (RhoA)/Rho-associated protein kinase (ROCK) pathway promotes leukocyte accumulation in tissue injury. However, it remains unknown whether Notch signaling regulates RhoA/ROCK-mediated immune responses in liver ischemia and reperfusion injury (IRI). This study investigated intracellular signaling pathways regulated by Notch receptors in the IR-stressed liver and in vitro...
October 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29023469/the-common-oncogenomic-program-of-notch1-and-notch3-signaling-in-t-cell-acute-lymphoblastic-leukemia
#4
Sung Hee Choi, Eric Severson, Warren S Pear, Xiaole S Liu, Jon C Aster, Stephen C Blacklow
Notch is a major oncogenic driver in T cell acute lymphoblastic leukemia (T-ALL), in part because it binds to an enhancer that increases expression of MYC. Here, we exploit the capacity of activated NOTCH1 and NOTCH3 to induce T-ALL, despite substantial divergence in their intracellular regions, as a means to elucidate a broad, common Notch-dependent oncogenomic program through systematic comparison of the transcriptomes and Notch-bound genomic regulatory elements of NOTCH1- and NOTCH3-dependent T-ALL cells...
2017: PloS One
https://www.readbyqxmd.com/read/29023247/mir-449a-a-potential-therapeutic-agent-for-cancer
#5
He Yong-Ming, Ji Ai-Jun, Xu Xiao-Yue, Lu Jian-Wei, Yu Chen, Chen Ye
MicroRNAs (miRNAs) have been reported to be associated with cancer progression and carcinogenesis. They are small, highly conserved, noncoding RNA molecules consisting of 19-25 nucleotides. By binding to complementary binding sites within the 3'-untranslated region of target mRNAs, miRNAs inhibit the translation of mRNAs or promote their degradation. miRNAs play critical roles in cancer initiation and development by functioning either as oncogenes or as tumor suppressors. Similarly, several studies have shown that miRNAs are involved in regulating various biological processes, including apoptosis, proliferation, cellular differentiation, signal transduction, and carcinogenesis...
October 11, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29021743/resolving-astrocyte-heterogeneity-in-the-cns
#6
REVIEW
W Todd Farmer, Keith Murai
Astrocytes play essential roles in nearly all aspects of brain function from modulating synapses and neurovasculature to preserving appropriate extracellular solute concentrations. To meet the complex needs of the central nervous system (CNS), astrocytes possess highly specialized properties that are optimized for their surrounding neural circuitry. Precisely how these diverse astrocytes types are generated in vivo, however, remains poorly understood. Key to this process is a critical balance of intrinsic developmental patterning and context-dependent environmental signaling events that configures astrocyte phenotype...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29018616/integration-of-lncrna-mirna-mrna-reveals-novel-insights-into-oviposition-regulation-in-honey-bees
#7
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/29016901/the-roles-of-the-sole-activator-type-auxin-response-factor-in-pattern-formation-of-marchantia-polymorpha
#8
Hirotaka Kato, Masaru Kouno, Mayuko Takeda, Hidemasa Suzuki, Kimitsune Ishizaki, Ryuichi Nishihama, Takayuki Kohchi
Cell division patterning is important to determine body shape in plants. Nuclear auxin signaling mediated by AUXIN RESPONSE FACTOR (ARF) transcription factors affects plant growth and development through regulation of cell division, elongation and differentiation. The evolutionary origin of the ARF-mediated pathway dates back to at least the common ancestor of bryophytes and other land plants. The liverwort Marchantia polymorpha has three phylogenetically distinct ARFs: MpARF1, the sole 'activator' ARF; and MpARF2 and MpARF3, two 'repressor' ARFs...
July 20, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28994095/repression-of-the-notch-pathway-prevents-liver-damage-in-streptozotocin-induced-diabetic-mice
#9
Eda Acikgoz, Huseyin Aktug, Gurkan Yigitturk, Kenan Demir, Ummu Guven, Fahriye Duzagac, Fatih Oltulu, Altug Yavasoglu, Gulperi Oktem
INTRODUCTION: Sunitinib is an oral inhibitor of vascular endothelial growth factor that is used to treat a variety of cancer. There are limited data regarding the effect of sunitinib on diabetes. In the liver, Notch signaling plays an important role in liver tissue development and homeostasis and its dysfunction is associated with liver pathologies. The aim of the present study is to investigate the effects of sunitinib on streptozotocin (STZ)-induced diabetic liver in mice models. MATERIAL AND METHODS: An experimental diabetes mellitus (DM) model was created in 28 male CD-1 mice...
October 10, 2017: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/28993437/thyroid-hormone-regulates-protease-expression-and-activation-of-notch-signaling-in-implantation
#10
Diletta Piccirilli, Enke Baldini, Micol Massimiani, Antonella Camaioni, Antonietta Salustri, Roberta Bernardini, Marco Centanni, Salvatore Ulisse, Constanzo Moretti, Luisa Campagnolo
A clinical association between thyroid dysfunction and pregnancy complications has been extensively reported, however the molecular mechanisms through which TH might regulate key-events of pregnancy have not been elucidated yet. In this respect, we performed in vivo studies in MMI- induced hypothyroid pregnant mice, evaluating the effect of hypothyroidism on the number of implantation sites, developing embryos/resorptions and pups per litter, at 4.5, 10.5, 18.5 days post coitum (dpc) and at birth. We also studied the expression of major molecules involved in implantation and placentation, such as the proteases ISPs, MMPs, TIMPs and Notch pathway related genes...
October 9, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28981589/notch-activation-by-shootin1-opposing-activities-on-2-ubiquitin-ligases
#11
Tamar Sapir, Talia Levy, Noga Kozer, Irina Shin, Vanessa Zamor, Rebecca Haffner-Krausz, Jane C McGlade, Orly Reiner
The evolutionarily conserved Notch pathway plays an important role in regulation of stem cell renewal and cell fate determination in numerous organs, and as such is a key pathway in normal health and disease processes. Canonical Notch signaling is usually activated by cell contact where transmembrane ligands such as Delta-like and Jagged bind to Notch receptors. Notch activation results in the translocation of the cleaved Notch intracellular domain (NICD) into the nucleus and subsequent activation of transcription...
July 13, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28979805/zinc-finger-rna-binding-protein-promotes-non-small-cell-carcinoma-growth-and-tumor-metastasis-by-targeting-the-notch-signaling-pathway
#12
Heng Zhang, Chun Fang Zhang, Ri Chen
Metastatic non-small-cell lung carcinoma (NSCLC) is typically incurable. The development of anti-metastatic therapies is hampered because the mechanisms regulating metastasis in NSCLC are not well known. Currently, there is no effective treatment for NSCLC once it has progressed to the metastatic stage. Therefore, further elucidation of the molecular mechanisms underlying the metastasis of NSCLC cells is urgently required for improving NSCLC treatment. Here, we report that the zinc finger RNA-binding protein (ZFR) is over-expressed in NSCLC cells and demonstrate that ZFR is a promising therapeutic target in metastatic NSCLC...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28978720/gamma-secretase-inhibition-by-bms-906024-enhances-efficacy-of-paclitaxel-in-lung-adenocarcinoma
#13
Katherine M Morgan, Bruce S Fischer, Francis Y Lee, Jamie J Shah, Joseph R Bertino, Jeffrey Rosenfeld, Amartya Singh, Hossein Khiabanian, Sharon R Pine
Notch signaling is aberrantly activated in approximately one third of non-small cell lung cancers (NSCLC). We characterized the interaction between BMS-906024, a clinically relevant Notch gamma secretase inhibitor (GSI), and front-line chemotherapy in preclinical models of NSCLC. Chemosensitivity assays were performed on 14 human NSCLC cell lines. There was significantly greater synergy between BMS-906024 and paclitaxel than BMS-906024 and cisplatin (mean CI value = 0.54 and 0.85, respectively, P = 0.01). On an extended panel of 31 NSCLC cell lines, 25 of which were adenocarcinoma, the synergy between BMS-906024 and paclitaxel was significantly greater in KRAS- and BRAF-wildtype than KRAS- or BRAF-mutant cells (mean CI = 0...
October 4, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28978094/dna-repair-deregulation-in-discrete-prostate-cancer-lesions-identified-on-multi-parametric-mri-and-targeted-by-mri-ultrasound-fusion-guided-biopsy
#14
Caleb R Dulaney, Soroush Rais-Bahrami, Debra Della Manna, Jennifer B Gordetsky, Jeffrey W Nix, Eddy S Yang
Prostate cancer is histologically and molecularly heterogeneous. Clinically significant disease is often driven by dominant intra-prostatic lesions (IPLs). Prostate cancers cluster into molecular phenotypes with substantial genetic heterogeneity making pathway-based molecular analysis appealing. MRI/ultrasound fusion biopsy provides a unique opportunity to characterize tumor biology of discrete lesions at diagnosis. This study determined the feasibility of pathway-based gene expression analysis of prostate biopsies and characterized cancer pathway deregulation...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977931/inhibition-of-notch-1-pathway-is-involved-in-rottlerin-induced-tumor-suppressive-function-in-nasopharyngeal-carcinoma-cells
#15
Yingying Hou, Shaoyan Feng, Lixia Wang, Zhe Zhao, Jingna Su, Xuyuan Yin, Nana Zheng, Xiuxia Zhou, Jun Xia, Zhiwei Wang
Recent studies have revealed that rottlerin is a natural chemical drug to exert its anti-cancer activity. However, the molecular mechanisms of rottlerin-induced tumor suppressive function have not been fully elucidated. Notch signaling pathway has been characterized to play a crucial role in tumorigenesis. Therefore, regulation of Notch pathway could be beneficial for the treatment of human cancer. The aims of our current study were to explore whether rottlerin could suppress Notch-1 expression, which leads to inhibition of cell proliferation, migration and invasion in nasopharyngeal carcinoma cells...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28974640/differential-interactions-between-notch-and-id-factors-control-neurogenesis-by-modulating-hes-factor-autoregulation
#16
Marcelo Boareto, Dagmar Iber, Verdon Taylor
During embryonic and adult neurogenesis, neural stem cells (NSCs) generate the correct number and types of neurons in a temporospatial fashion. Control of NSC activity and fate is crucial for brain formation and homeostasis. Neurogenesis in the embryonic and adult brain differ considerably, but Notch signaling and inhibitor of DNA-binding (ID) factors are pivotal in both. Notch and ID factors regulate NSC maintenance; however, it has been difficult to evaluate how these pathways potentially interact. Here, we combined mathematical modeling with analysis of single-cell transcriptomic data to elucidate unforeseen interactions between the Notch and ID factor pathways...
October 1, 2017: Development
https://www.readbyqxmd.com/read/28973690/early-life-exposure-to-low-levels-of-ahr-agonist-pcb126-3-3-4-4-5-pentachlorobiphenyl-reprograms-gene-expression-in-adult-brain
#17
Neelakanteswar Aluru, Sibel I Karchner, Lilah Glazer
Early life exposure to environmental chemicals can have long-term consequences that are not always apparent until later in life. We recently demonstrated that developmental exposure of zebrafish to low, non-embryotoxic levels of 3,3',4,4',5-pentachlorobiphenyl (PCB126) did not affect larval behavior, but caused changes in adult behavior. The objective of this study was to investigate the underlying molecular basis for adult behavioral phenotypes resulting from early life exposure to PCB126. We exposed zebrafish embryos to PCB126 during early development and measured transcriptional profiles in whole embryos, larvae and adult male brains using RNA-sequencing...
September 9, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28972999/effects-of-insulin-like-growth-factors-on-early-embryonic-chick-limb-myogenesis
#18
Rabeea Hazim Mohammed, Helen Anderton, John Michael Brameld, Dylan Sweetman
Limb muscles derive from pax3 expressing precursor cells that migrate from the hypaxial somite into the developing limb bud. Once there they begin to differentiate and express muscle determination genes such as MyoD. This process is regulated by a combination of inductive or inhibitory signals including Fgf18, retinoic acid, HGF, Notch and IGFs. IGFs are well known to affect late stages of muscle development and to promote both proliferation and differentiation. We examined their roles in early stage limb bud myogenesis using chicken embryos as an experimental model...
2017: PloS One
https://www.readbyqxmd.com/read/28971991/targeted-gamma-secretase-inhibition-of-notch-signaling-activation-in-acute-renal-injury
#19
Jean-Christophe Wyss, Rajesh Kumar, Josip Mikulic, Manfred Schneider, Johannes D Aebi, Lucienne Juillerat-Jeanneret, Dela Golshayan
The Notch pathway has been reported to control tissue damage in acute kidney diseases. To investigate potential beneficial nephroprotective effects of targeting Notch, we developed chemically functionalized γ-secretase inhibitors (GSIs) targeting γ-glutamyltranspeptidase (γ-GT) and/or γ-glutamylcyclotransfase (γ-GCT), two enzymes overexpressed in the injured kidney, and evaluated them in in vivo murine models of acute tubular and glomerular damage. Exposure of the animals to disease-inducing drugs together with the functionalized GSIs improved proteinuria and, to some extent, kidney dysfunction...
September 27, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28969930/do-as-i-say-not-ch-as-i-do-lateral-control-of-cell-fate
#20
REVIEW
Marika Sjöqvist, Emma R Andersson
Breaking symmetry in populations of uniform cells, to induce adoption of an alternative cell fate, is an essential developmental mechanism. Similarly, domain and boundary establishment are crucial steps to forming organs during development. Notch signaling is a pathway ideally suited to mediating precise patterning cues, as both receptors and ligands are membrane-bound and can thus act as a precise switch to toggle cell fates on or off. Fine-tuning of signaling by positive or negative feedback mechanisms dictate whether signaling results in lateral induction or lateral inhibition, respectively, allowing Notch to either induce entire regions of cell specification, or dictate binary fate choices...
September 29, 2017: Developmental Biology
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