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https://www.readbyqxmd.com/read/28337369/role-of-notch-signaling-pathway-in-pancreatic-cancer
#1
REVIEW
Jiankun Gao, Bo Long, Zhiwei Wang
Pancreatic cancer (PC) is one of the highly aggressive malignancies in the United States. It has been shown that multiple signaling pathways are involved in the pathogenesis of PC, such as JNK, PI3K/AKT, Rho GTPase, Hedgehog (Hh) and Skp2. In recent years, accumulated evidence has demonstrated that Notch signaling pathway plays critical roles in the development and progression of PC. Therefore, in this review we discuss the recent literature regarding the function and regulation of Notch in the pathogenesis of PC...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28327358/a-cell-autonomous-positive-signaling-circuit-associated-with-the-pdgf-no-id4-regulatory-axis-in-glioblastoma-cells
#2
Kiyoung Eun, Hye-Min Jeon, Sung-Ok Kim, Sang-Hun Choi, Seon Yong Lee, Xiong Jin, Sung-Chan Kim, Hyunggee Kim
Most cancer-related signaling pathways sustain their active or inactive status via genetic mutations or various regulatory mechanisms. Previously, we demonstrated that platelet-derived growth factor (PDGF) activates Notch signaling through nitric oxide (NO)-signaling-driven activation of inhibitor of differentiation 4 (ID4) in glioblastoma (GBM) stem cells (GSCs) and endothelial cells in the vascular niche of GBM, leading to maintenance of GSC traits and GBM progression. Here, we determined that the PDGF-NO-ID4-signaling axis is constantly activated through a positive regulatory circuit...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28323021/the-challenge-of-targeting-cancer-stem-cells-to-halt-metastasis
#3
REVIEW
Alice Agliano, Alfonso Calvo, Carol Box
Despite a continuing debate about the existence of cancer stem cells (CSCs), recent discoveries have provided further support for their existence and their roles in drug resistance, cancer recurrence and metastasis. CSC characteristics, such as self-renewal and tumour initiation, and supporting cellular processes, particularly the epithelial-to-mesenchymal transition, are attracting a great deal of attention from cancer researchers as they offer opportunities for discovering novel therapeutic targets for future drug development...
March 16, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28322442/systems-analysis-of-dynamic-transcription-factor-activity-identifies-targets-for-treatment-in-olaparib-resistant-cancer-cells
#4
Joseph T Decker, Eric C Hobson, Yining Zhang, Seungjin Shin, Alexandra L Thomas, Jacqueline S Jeruss, Kelly B Arnold, Lonnie D Shea
The development of resistance to targeted therapeutics is a challenging issue for the treatment of cancer. Cancers that have mutations in BRCA, a DNA repair protein, have been treated with poly (ADP-ribose) polymerase (PARP) inhibitors, which target a second DNA repair mechanism with the aim of inducing synthetic lethality. While these inhibitors have shown promise clinically, the development of resistance can limit their effectiveness as a therapy. This study investigated mechanisms of resistance in BRCA-mutated cancer cells (HCC1937) to Olaparib (AZD2281) using TRACER, a technique for measuring dynamics of transcription factor (TF) activity in living cells...
March 21, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28320827/structural-and-chemical-biology-of-presenilin-complexes
#5
Douglas S Johnson, Yue-Ming Li, Martin Pettersson, Peter H St George-Hyslop
The presenilin proteins are the catalytic subunits of a tetrameric complex containing presenilin 1 or 2, anterior pharynx defective 1 (APH1), nicastrin, and PEN-2. Other components such as TMP21 may exist in a subset of specialized complexes. The presenilin complex is the founding member of a unique class of aspartyl proteases that catalyze the γ, ɛ, ζ site cleavage of the transmembrane domains of Type I membrane proteins including amyloid precursor protein (APP) and Notch. Here, we detail the structural and chemical biology of this unusual enzyme...
March 20, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28319529/the-notch-signaling-system-is-involved-in-the-regulation-of-reparative-angiogenesis-in-the-zone-of-stasis
#6
Ozan Luay Abbas, Orhan Özatik, Yunus Kasm Terzi, Fikriye Yasemin Özatik, Rukiye Nar, Gamze Turna
The Notch pathway ligand Delta-like 4 (Dll4) functions as an antiangiogenic factor, inhibiting vascular endothelial growth factor (VEGF)-induced angiogenesis. This function is documented in tumor and embryonic vasculature. However, its implication in burn wounds remains unexplored. Our objective was to explore the involvement of the Notch in the healing of zone of stasis burns. We hypothesized that anti-Dll4 therapy would prevent progressive necrosis in the stasis zone by promoting angiogenesis. Burns were created in 21 rats using the comb burn model...
March 13, 2017: Journal of Burn Care & Research: Official Publication of the American Burn Association
https://www.readbyqxmd.com/read/28294046/notch-signalling-pathways-and-their-importance-in-the-treatment-of-cancers
#7
Seong Lin Teoh, Srijit Das
The Notch pathway is an evolutionarily conserved, intercellular signalling system which is present in all multicellular organisms and mammals. The Notch pathway plays an important role in the embryonic development as it controls cell proliferation, cell differentiation and binary cell fate decisions. In the present review, we discuss the Notch signalling pathway components i.e. Notch receptors, ligands, effector, and their regulators. Interestingly, the Notch signalling pathway is dysregulated in many cancers...
March 9, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28286920/blockade-of-notch-signaling-promotes-acetaminophen-induced-liver-injury
#8
Longfeng Jiang, Michael Ke, Shi Yue, Wen Xiao, Youde Yan, Xiaozhao Deng, Qi-Long Ying, Jun Li, Bibo Ke
Liver injury after experimental acetaminophen treatment is mediated both by direct hepatocyte injury through a P450-generated toxic metabolite and indirectly by activated liver Kupffer cells and neutrophils. This study was designed to investigate the role of Notch signaling in the regulation of innate immune responses in acetaminophen (APAP)-induced liver injury. Using a mouse model of APAP-induced liver injury, wild-type (WT) and toll-like receptor 4 knockout (TLR4 KO) mice were injected intraperitoneally with APAP or PBS...
March 13, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28280276/regulation-of-pi3k-signaling-in-t-cell-acute-lymphoblastic-leukemia-a-novel-pten-ikaros-mir-26b-mechanism-reveals-a-critical-targetable-role-for-pik3cd
#9
T Yuan, Y Yang, J Chen, W Li, W Li, Q Zhang, Y Mi, R S Goswami, J Q You, D Lin, M D Qian, S Calin, Y Liang, R N Miranda, G A Calin, X Zhou, L Ma, P A Zweidler-Mc, B Liu, A P Weng, L J Medeiros, Y Zhang, M J You
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy, and T-ALL patients are prone to early disease relapse and suffer from poor outcomes. The PTEN, PI3K/AKT, and Notch pathways are frequently altered in T-ALL. PTEN is a tumor suppressor that inactivates the PI3K pathway. We profiled miRNAs in Pten-deficient mouse T-ALL and identified miR-26b as a potentially dysregulated gene. We validated decreased expression levels of miR-26b in mouse and human T-ALL cells. In addition, expression of exogenous miR-26b reduced proliferation and promoted apoptosis of T-ALL cells in vitro, and hindered progression of T-ALL in vivo...
March 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28279221/notch-signaling-plays-a-crucial-role-in-cancer-stem-like-cells-maintaining-stemness-and-mediating-chemotaxis-in-renal-cell-carcinoma
#10
Wei Xiao, Zhiyong Gao, Yixing Duan, Wuxiong Yuan, Yang Ke
BACKGROUND: Cancer stem cells (CSCs) are correlated with the initiation, chemoresistance and relapse of tumors. Notch pathway has been reported to function in CSCs maintenance, but whether it is involved in renal cell carcinoma (RCC) CSCs maintaining stemness remain unclear. This study aims to explore the effect of Notch pathway on stemness of CSCs in RCC and the underlying mechanisms. METHODS: The CD133(+)/CD24(+) cells were isolated from RCC ACHN and Caki-1 cell line using Magnetic-activated cell sorting and identified by Flow cytometry analysis...
March 9, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28278384/characterization-of-endogenous-nitric-oxide-role-in-myogenic-vascular-oscillations-during-cooling-evoked-hemodynamic-perturbations-of-rats
#11
Yi-Hsien Lin, Yia-Ping Liu, Yu-Chieh Lin, Po-Lei Lee, Che-Se Tung
Rapid immersion of a rat's limbs into 4°C water, a model of cold stress (CS), can elicit hemodynamic perturbations (CEHP). We have reported that CEHP is highly relevant to the sympathetic activation and nitric oxide production. This study identifies the role of nitric oxide in CEHP. Conscious rats were pretreated with the nitric oxide synthase inhibitor L-NAME alone or following the removal of sympathetic influences using hexamethonium or guanethidine, and then they were subjected to a 10-min CS trial. Hemodynamic indices were telemetrically monitored throughout the experiment...
March 9, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28277073/enhancement-of-vascular-endothelial-growth-factor-s-angiogenic-capacity-by-the-therapeutic-modulation-of-notch-signalling-improves-tram-flap-survival-in-rats-submitted-to-nicotine
#12
Ozan Luay Abbas, Yunus Kasım Terzi, Orhan Özatik, Fikriye Yasemin Özatik, Gamze Turna, Rukiye Nar, Ahmet Musmul
BACKGROUND: Smoke of cigarettes, and specifically nicotine, has been shown to diminish pedicled transverse rectus abdominis musculocutaneous (TRAM) flap survival. Considering that Notch signalling through its ligand Delta-like 4 (Dll4) functions as anti-angiogenic factor by inhibiting the pro-angiogenic effects of vascular endothelial growth factor (VEGF), it is hypothesised that inhibition of the Notch would promote angiogenesis and increase TRAM flap survival in rats submitted to nicotine...
February 13, 2017: Journal of Plastic Surgery and Hand Surgery
https://www.readbyqxmd.com/read/28275186/cpg-in-combination-with-an-inhibitor-of-notch-signaling-suppresses-fi-rsv-enhanced-airway-hyperresponsiveness-and-inflammation-through-inhibiting-th17-memory-responses-and-promoting-tissue-resident-memory-cells-in-lungs
#13
Lei Zhang, Hongyong Li, Yan Hai, Wei Yin, Wenjian Li, Boyang Zheng, Xiaomin Du, Na Li, Zhengzheng Zhang, Yuqing Deng, Ruihong Zeng, Lin Wei
Respiratory syncytial virus (RSV) is the leading cause of childhood hospitalizations. The formalin-inactivated RSV (FI-RSV) vaccine enhanced respiratory disease (ERD) has been an obstacle to the development of a safe and effective killed RSV vaccine. Agonists of Toll-like receptor (TLR) have been shown to regulate immune responses induced by FI-RSV. Notch signaling plays critical roles during the differentiation and effector function phases of innate and adaptive immune responses. Cross-talk between TLR and Notch signaling pathways results in fine tuning of TLR-triggered innate inflammatory responses...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28275151/antagonism-of-egfr-and-notch-limits-resistance-to-egfr-inhibitors-and-radiation-by-decreasing-tumor-initiating-cell-frequency
#14
Shi Hu, Wenyan Fu, Tian Li, Qingning Yuan, Feifei Wang, Gaojian Lv, Yuanyuan Lv, Xiaoyan Fan, Yafeng Shen, Fangxing Lin, Ying Tang, Xuting Ye, Yongji Yang, Changhai Lei
Epidermal growth factor receptor (EGFR) blockade and radiation are efficacious in the treatment of cancer, but resistance is commonly reported. Studies have suggested that dysregulation of Notch signaling and enrichment of the cancer stem cell population underlie these treatment challenges. Our data show that dual targeting of EGFR and Notch2/3 receptors with antibody CT16 not only inhibited signaling mediated by these receptors but also showed a strong anti-stem cell effect both in vitro and in vivo. Treatment with CT16 prevented acquired resistance to EGFR inhibitors and radiation in non-small cell lung cancer (NSCLC) cell line models and patient-derived xenograft tumors...
March 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28272325/c-myc-induced%C3%A2-survivin%C3%A2-is%C3%A2-essential%C3%A2-for%C3%A2-promoting%C3%A2-the%C3%A2-notch-dependent%C3%A2-t%C3%A2-cell%C3%A2-differentiation%C3%A2-from%C3%A2-hematopoietic%C3%A2-stem%C3%A2-cells
#15
Rizwanul Haque, Jianyong Song, Mohammad Haque, Fengyang Lei, Praneet Sandhu, Bing Ni, Songguo Zheng, Deyu Fang, Jin-Ming Yang, Jianxun Song
Notch is indispensable for T cell lineage commitment, and is needed for thymocyte differentiation at early phases. During early stages of T cell development, active Notch prevents other lineage potentials including B cell lineage and myeloid cell (e.g., dendritic cell) lineage. Nevertheless, the precise intracellular signaling pathways by which Notch promotes T cell differentiation remain unclear. Here we report that the transcription factor c-Myc is a key mediator of the Notch signaling-regulated T cell differentiation...
March 6, 2017: Genes
https://www.readbyqxmd.com/read/28270494/blockade-of-deubiquitylating-enzyme-usp1-inhibits-dna-repair-and-triggers-apoptosis-in-multiple-myeloma-cells
#16
Deepika Sharma Das, Abhishek Das, Arghya Ray, Yan Song, Mehmet K Samur, Nikhil C Munshi, Dharminder Chauhan, Kenneth C Anderson
PURPOSE: The ubiquitin proteasome pathway is a validated therapeutic target in multiple myeloma (MM). Deubiquitylating enzyme USP1 participates in DNA damage response and cellular differentiation pathways. To date, the role of USP1 in MM biology is not defined. In the present study, we investigated the functional significance of USP1 in MM using genetic and biochemical approaches. EXPERIMENTAL DESIGN: To investigate the role of USP1 in myeloma, we utilized USP1 inhibitor SJB3-019A (SJB) for studies in myeloma cell lines and patient MM cells...
March 7, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28262548/notch-inhibition-enhances-cardiac-reprogramming-by-increasing-mef2c-transcriptional-activity
#17
Maria Abad, Hisayuki Hashimoto, Huanyu Zhou, Maria Gabriela Morales, Beibei Chen, Rhonda Bassel-Duby, Eric N Olson
Conversion of fibroblasts into functional cardiomyocytes represents a potential means of restoring cardiac function after myocardial infarction, but so far this process remains inefficient and little is known about its molecular mechanisms. Here we show that DAPT, a classical Notch inhibitor, enhances the conversion of mouse fibroblasts into induced cardiac-like myocytes by the transcription factors GATA4, HAND2, MEF2C, and TBX5. DAPT cooperates with AKT kinase to further augment this process, resulting in up to 70% conversion efficiency...
March 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28257582/osthole-prevents-cerebral-ischemia-reperfusion-injury-via-notch-signaling-pathway
#18
Junhong Guan, Xiangtai Wei, Shengtao Qu, Tao Lv, Qiang Fu, Ye Yuan
Stroke is a common cerebrovascular disease in aged population with the second leading mortality and the leading cause of permanent disability, and the ischemic stroke is the primary form. Osthole is a coumarin derivative extracted from the fruits of Cnidium monnieri (Linn.) Cuss. In this study, we established the rat middle cerebral artery occlusion/reperfusion (MCAO/R) model in vivo, and found that MCAO/R caused cerebral infarction, hippocampus neuronal injury and apoptosis, and also activated the Notch 1 signaling pathway...
March 3, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28256007/targeting-notch-activated-m1-macrophages-attenuates-joint-tissue-damage-in-a-mouse-model-of-inflammatory-arthritis
#19
Wen Sun, Hengwei Zhang, Hua Wang, Yahui Grace Chiu, Christopher T Ritchlin, Amy Kiernan, Brendan F Boyce, Lianping Xing
Expression of Notch signaling molecules are increased in synovium from patients with rheumatoid arthritis (RA). However, it is not known which cell type(s) in RA synovium have Notch activation or if they play a pathogenetic role in RA. Here, we used Hes1-GFP/TNF-transgenic (TNF-Tg) mice to investigate the role of cells with active Notch signaling (GFP +) in RA. The number of GFP+ cells was significantly increased in synovium in Hes1-GFP/TNF-Tg mice and about 60% of them were F4/80+ macrophages expressing the inflammatory macrophage (M1) marker...
March 3, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28255276/melatonin-inhibits-glioblastoma-stem-like-cells-through-suppression-of-ezh2-notch1-signaling-axis
#20
Xiangrong Zheng, Bo Pang, Guangyan Gu, Taihong Gao, Rui Zhang, Qi Pang, Qian Liu
Glioblastoma stem-like cells (GSCs) play essential roles in glioma growth, radio- and chemo-resistance, and recurrence. Elimination of GSCs has therefore become a key strategy and challenge in glioblastoma therapy. Here, we show that melatonin, an indolamine derived from I-tryptophan, significantly inhibited viability and self-renewal ability of GSCs accompanied by a decrease of stem cell markers. We have identified EZH2-NOTCH1 signaling as the key signal pathway that regulated the effects of melatonin in the GSCs...
2017: International Journal of Biological Sciences
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