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https://www.readbyqxmd.com/read/28086833/delta-like-4-notch-signaling-promotes-apc-min-tumor-initiation-through-angiogenic-and-non-angiogenic-related-mechanisms
#1
Marina Badenes, Alexandre Trindade, Hugo Pissarra, Luís Lopes-da-Costa, António Duarte
BACKGROUND: Delta like 4 (Dll4)/Notch signaling is a key regulator of tumor angiogenesis. Additionally, the role of Dll4 has been studied on tumor stem cells. However, as these cells are implicated in tumor angiogenesis, it is conceivable that the effect of Dll4 on these cells may be a consequence of its angiogenic function. Our aim was to evaluate the expression and dissect the functions of Dll4 in the Apc (Min/+) model of colorectal cancer. METHODS: We evaluated the protein expression pattern of Dll4 and other Notch members in the Apc (Min/+) tumors relatively to the normal gut and compared endothelial-specific with ubiquitous Dll4 knockout mice on an Apc (Min/+) background...
January 13, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28079885/mirna182-regulates-percentage-of-myeloid-and-erythroid-cells-in-chronic-myeloid-leukemia
#2
Deepak Arya, Sasikala P Sachithanandan, Cecil Ross, Dasaradhi Palakodeti, Shang Li, Sudhir Krishna
The deregulation of lineage control programs is often associated with the progression of haematological malignancies. The molecular regulators of lineage choices in the context of tyrosine kinase inhibitor (TKI) resistance remain poorly understood in chronic myeloid leukemia (CML). To find a potential molecular regulator contributing to lineage distribution and TKI resistance, we undertook an RNA-sequencing approach for identifying microRNAs (miRNAs). Following an unbiased screen, elevated miRNA182-5p levels were detected in Bcr-Abl-inhibited K562 cells (CML blast crisis cell line) and in a panel of CML patients...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28058624/zebrafish-phenotypic-screen-identifies-novel-notch-antagonists
#3
Vithya Velaithan, Kazuhide Shaun Okuda, Mei Fong Ng, Norazwana Samat, Sze Wei Leong, Siti Munirah Mohd Faudzi, Faridah Abas, Khozirah Shaari, Sok Ching Cheong, Pei Jean Tan, Vyomesh Patel
Zebrafish represents a powerful in vivo model for phenotype-based drug discovery to identify clinically relevant small molecules. By utilizing this model, we evaluated natural product derived compounds that could potentially modulate Notch signaling that is important in both zebrafish embryogenesis and pathogenic in human cancers. A total of 234 compounds were screened using zebrafish embryos and 3 were identified to be conferring phenotypic alterations similar to embryos treated with known Notch inhibitors...
January 5, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28051360/the-notch-ligand-jag1-regulates-gdnf-expression-in-sertoli-cells
#4
Thomas Xavier Garcia, Parag Parekh, Pooja Gandhi, Krishna M Sinha, Marie-Claude Hofmann
In the seminiferous epithelium of the testis, Sertoli cells are key niche cells directing proliferation and differentiation of spermatogonial stem cells (SSCs) into spermatozoa. Sertoli cells produce glial cell line-derived neurotrophic factor (GDNF), which is essential for SSC self-renewal and progenitor expansion. While the role of GDNF in the testis stem cell niche is established, little is known about how this factor is regulated. Our previous studies on NOTCH activity in Sertoli cells demonstrated a role of this pathway in limiting stem/progenitor cell numbers, thus ultimately down-regulating sperm cell output...
January 4, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28035539/brucine-inhibits-bone-metastasis-of-breast-cancer-cells-by-suppressing-jagged1-notch1-signaling-pathways
#5
Ke-Fei Hu, Xiang-Ying Kong, Mi-Cun Zhong, Hong-Ye Wan, Na Lin, Xiao-Hua Pei
OBJECTIVE: To examine the effects of brucine on the invasion, migration and bone resorption of receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis. METHODS: The osteoclastogenesis model was builded by co-culturing human breast tumor MDA-MB-231 and mouse RAW264.7 macrophages cells. RANKL (50 ng/mL) and macrophage-colony stimulating factor (50 ng/mL) were added to this system, followed by treatment with brucine (0.02, 0.04 and 0...
December 29, 2016: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28028172/histone-deacetylase-1-is-essential-for-rod-photoreceptor-differentiation-by-regulating-acetylation-at-histone-h3-lysine-9-and-histone-h4-lysine-12-in-the-mouse-retina
#6
Renata C Ferreira, Evgenya Y Popova, Jessica James, Marcelo Rs Briones, Samuel S Zhang, Colin J Barnstable
Histone acetylation has a regulatory role in gene expression and is necessary for proper tissue development. To investigate the specific roles of histone deacetylases (HDACs) in rod differentiation in neonatal mouse retinas we used a pharmacological approach which showed that inhibition of class I but not class IIa HDACs caused the same phenotypic changes seen with broad spectrum HDAC inhibitors, most notably a block in the differentiation of rod photoreceptors. Inhibition of HDAC1 resulted in increase of acetylation of lysine 9 of histone 3 (H3K9) and lysine 12 of histone 4 (H4K12), but not lysine 27 of histone 3 (H3K27), and led to maintained expression of progenitor-specific genes such as Vsx2 and Hes1 with concomitant block of expression of rod-specific genes...
December 27, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28019674/hairy-and-enhancer-of-split-related-with-yrpw-motif-like-heyl-is-dispensable-for-bone-remodeling-in-mice
#7
Ernesto Canalis, Stefano Zanotti
Notch induces Hairy Enhancer of Split (Hes)1 and Hes-related with YRPW motif (Hey) Hey1, Hey2 and Hey-like (HeyL) expression in osteoblasts, but it is not known whether any of these target genes mediates the effect of Notch in the skeleton. We demonstrated that Notch1 activation in osteoblasts/osteocytes induces Hes1, Hey1, Hey2 and HeyL, but HeyL was induced to a greater extent than other target genes. To characterize HeyL null mice for their skeletal phenotype, microcomputed tomography (µCT) and histomorphometric analysis of HeyL null and sex-matched littermate controls was performed...
December 26, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28013292/mib2-variants-altering-notch-signalling-result-in-left-ventricle-hypertrabeculation-non-compaction-and-are-associated-with-m%C3%A3-n%C3%A3-trier-like-gastropathy
#8
Pasquale Piccolo, Sergio Attanasio, Ilaria Secco, Riccardo Sangermano, Caterina Strisciuglio, Giuseppe Limongelli, Erasmo Miele, Margherita Mutarelli, Sandro Banfi, Vincenzo Nigro, Tirso Pons, Alfonso Valencia, Lorena Zentilin, Severo Campione, Gerardo Nardone, Ty C Lynnes, Patricia B S Celestino-Soper, Katherine G Spoonamore, Francesco P D'Armiento, Mauro Giacca, Annamaria Staiano, Matteo Vatta, Chiara Collesi, Nicola Brunetti-Pierri
We performed whole exome sequencing in individuals from a family with autosomal dominant gastropathy resembling Ménétrier disease, a premalignant gastric disorder with epithelial hyperplasia and enhanced EGFR signalling. Ménétrier disease is believed to be an acquired disorder, but its aetiology is unknown. In affected members, we found a missense p.V742G variant in MIB2, a gene regulating NOTCH signalling that has not been previously linked to human diseases. The variant segregated with the disease in the pedigree, affected a highly conserved amino acid residue, and was predicted to be deleterious although it was found with a low frequency in control individuals...
December 23, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28003475/single-cell-transcriptomics-reveals-unanticipated-features-of-early-hematopoietic-precursors
#9
Jennifer Yang, Yoshiaki Tanaka, Montrell Seay, Zhen Li, Jiaqi Jin, Lana Xia Garmire, Xun Zhu, Ashley Taylor, Weidong Li, Ghia Euskirchen, Stephanie Halene, Yuval Kluger, Michael P Snyder, In-Hyun Park, Xinghua Pan, Sherman Morton Weissman
Molecular changes underlying stem cell differentiation are of fundamental interest. scRNA-seq on murine hematopoietic stem cells (HSC) and their progeny MPP1 separated the cells into 3 main clusters with distinct features: active, quiescent, and an un-characterized cluster. Induction of anemia resulted in mobilization of the quiescent to the active cluster and of the early to later stage of cell cycle, with marked increase in expression of certain transcription factors (TFs) while maintaining expression of interferon response genes...
December 20, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27982686/the-expression-levels-of-notch-related-signaling-molecules-in-pulmonary-microvascular-endothelial-cells-in-bleomycin-induced-rat-pulmonary-fibrosis
#10
Qian Yin, Weihua Wang, Guangbin Cui, Haiyan Nan, Linfeng Yan, Wenhu Zhang, Song Zhang, Jingguo Wei
Previous studies have suggested that the Notch signaling pathway plays a very important role in the proliferation and differentiation of pulmonary microvascular endothelial cells (PMVECs). Therefore, we aimed to investigate the expression level of Notch-related signaling molecules in PMVECs in bleomycin (BLM)-induced rat pulmonary fibrosis. Immunohistochemistry, immunofluorescence, western blotting, and real-time PCR were used to analyze the differences in protein and mRNA expression levels of Notch-related signaling molecules, i...
December 16, 2016: Physiological Research
https://www.readbyqxmd.com/read/27981247/aspartate-%C3%AE-hydroxylase-asph-a-potential-therapeutic-target-in-human-malignant-gliomas
#11
Lisa-Marie Sturla, Ming Tong, Nick Hebda, Jinsong Gao, John-Michael Thomas, Mark Olsen, Suzanne M de la Monte
BACKGROUND: Despite therapeutic advances, survival with glioblastoma multiforme (GBM) remains below 15 months from diagnosis due to GBM's highly infiltrative nature which precludes complete surgical resection. Patient outcomes could potentially be improved by targeting genes and pathways that drive neoplastic cell motility and invasiveness, including hypoxia-inducible factor-1 (HIF-1α), NOTCH, and aspartate-β-hydroxylase (ASPH). METHODS: Human astrocytoma biopsy specimens (n = 37), WHO Grades II-IV, were analyzed for levels and distributions of ASPH and HIF-1α immunoreactivity by immunohistochemical staining, and ASPH, Notch, JAG, HES1, HEY1 and HIF1α mRNA expression by quantigene multiplex analysis...
December 2016: Heliyon
https://www.readbyqxmd.com/read/27966788/notch-signaling-participates-in-tgf-%C3%AE-induced-sost-expression-under-intermittent-compressive-stress
#12
Jeeranan Manokawinchoke, Piyamas Sumrejkanchanakij, Prasit Pavasant, Thanaphum Osathanon
Notch signaling is regulated by mechanical stimuli in various cell types. It has previously been reported that intermittent compressive stimuli enhanced sclerostin (SOST) expression in human periodontal ligament cells (hPDLs) by regulating transforming growth factor-β (TGF-β) expression. The aim of the present study was to determine the involvement of Notch signaling in the TGF-β induced SOST expression in hPDLs. Cells were treated with intermittent compressive stress in a computer-controlled apparatus for 24 h...
December 14, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27942853/notch-signaling-mediated-cell-to-cell-interaction-is-dependent-on-e-cadherin-adhesion-in-adult-rat-anterior-pituitary
#13
Khongorzul Batchuluun, Morio Azuma, Takashi Yashiro, Motoshi Kikuchi
The rat anterior pituitary is composed of hormone-producing cells, non-hormone-producing cells (referred to as folliculostellate cells) and marginal layer cells. In the adult rat, progenitor cells of hormone-producing cells have recently been reported to be maintained within this non-hormone-producing cell population. In tissue, non-hormone-producing cells construct homophilic cell aggregates by the differential expression of the cell adhesion molecule E-cadherin. We have previously shown that Notch signaling, a known regulator of progenitor cells in a number of organs, is activated in the cell aggregates...
December 10, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27939883/indispensable-role-of-notch-ligand-dependent-signaling-in-the-proliferation-and-stem-cell-niche-maintenance-of-apc-deficient-intestinal-tumors
#14
Toru Nakata, Hiromichi Shimizu, Sayaka Nagata, Go Ito, Satoru Fujii, Kohei Suzuki, Ami Kawamoto, Fumiaki Ishibashi, Reiko Kuno, Sho Anzai, Tatsuro Murano, Tomohiro Mizutani, Shigeru Oshima, Kiichiro Tsuchiya, Tetsuya Nakamura, Katsuto Hozumi, Mamoru Watanabe, Ryuichi Okamoto
Ligand-dependent activation of Notch signaling is required to maintain the stem-cell niche of normal intestinal epithelium. However, the precise role of Notch signaling in the maintenance of the intestinal tumor stem cell niche and the importance of the RBPJ-independent non-canonical pathway in intestinal tumors remains unknown. Here we show that Notch signaling was activated in LGR5(+ve) cells of APC-deficient mice intestinal tumors. Accordingly, Notch ligands, including Jag1, Dll1, and Dll4, were expressed in these tumors...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27939630/endosulfan-inhibits-proliferation-through-the-notch-signaling-pathway-in-human-umbilical-vein-endothelial-cells
#15
Jialiu Wei, Lianshuang Zhang, Lihua Ren, Jin Zhang, Yang Yu, Ji Wang, Junchao Duan, Cheng Peng, Zhiwei Sun, Xianqing Zhou
Our previous research showed that endosulfan triggers the extrinsic coagulation pathway by damaging endothelial cells and causes hypercoagulation of blood. To identify the mechanism of endosulfan-impaired endothelial cells, we treated human umbilical vein endothelial cells (HUVECs) with different concentrations of endosulfan, with and without an inhibitor for Notch, N-[N-(3, 5-difluorophenacetyl)-1-alanyl]S-Phenylglycinet-butylester (DAPT, 20 μM), or a reactive oxygen species (ROS) scavenger, N-Acetyl-l-cysteine (NAC, 3 mM), for 24 h...
February 2017: Environmental Pollution
https://www.readbyqxmd.com/read/27923595/vitamin-d-compounds-inhibit-cancer-stem-like-cells-and-induce-differentiation-in-triple-negative-breast-cancer
#16
REVIEW
Naing Lin Shan, Joseph Wahler, Hong Jin Lee, Min Ji Bak, Soumyasri Das Gupta, Hubert Maehr, Nanjoo Suh
Triple-negative breast cancer is one of the least responsive breast cancer subtypes to available targeted therapies due to the absence of hormonal receptors, aggressive phenotypes, and the high rate of relapse. Early breast cancer prevention may therefore play an important role in delaying the progression of triple-negative breast cancer. Cancer stem cells are a subset of cancer cells that are thought to be responsible for tumor progression, treatment resistance, and metastasis. We have previously shown that vitamin D compounds, including a Gemini vitamin D analog BXL0124, suppress progression of ductal carcinoma in situ in vivo and inhibit cancer stem-like cells in MCF10DCIS mammosphere cultures...
December 5, 2016: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27916094/-knockdown-of-runx3-inhibits-hypoxia-induced-endothelial-to-mesenchymal-transition-of-human-cardiac-microvascular-endothelial-cells
#17
Yanhua Liu, Bingong Li, Yuqin Wang, Delong Wang, Jin Zou, Xuan Ke, Yanqin Hao
Objective To investigate the effects of Runt-related transcription factor 3 (RUNX3) knockdown on hypoxia-induced endothelial-to-mesenchymal transition (EndoMT) of human cardiac microvascular endothelial cells (HCMECs), and elucidate the underlying molecular mechanism. Methods HCMECs were cultured in hypoxic conditions and infected with RUNX3-RNAi lentivirus to knock-down the expression of RUNX3. Reverse transcription PCR was performed to detect the mRNA expressions of RUNX3 and EndoMT related genes such as CD31, vascular endothelial cadherin (VE-cadherin), α-smooth muscle actin (α-SMA) and fibroblast-specific protein-1 (FSP-1); Western blotting was used to determine the protein expressions of RUNX3, CD31, α-SMA and another molecules involved in EndoMT; and immunofluorescence cytochemistry was applied to observe the colocalization of CD31 and α-SMA...
December 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27908834/gamma-secretase-inhibitor-impairs-epithelial-to-mesenchymal-transition-induced-by-tgf-%C3%AE-in-ovarian-tumor-cell-lines
#18
M C Pazos, D Abramovich, A Bechis, P Accialini, F Parborell, M Tesone, G Irusta
Ovarian cancer is characterized by being highly metastatic, a feature that represents the main cause of failure of the treatment. This study investigated the effects of γ-secretase inhibition on the TGF-β-induced epithelial-mesenchymal transition (EMT) process in ovarian cancer cell lines. SKOV3 cells incubated in the presence of TGF-β showed morphological and biochemical changes related to EMT, which were blocked by co-stimulation with TGF-β and the γ-secretase inhibitor DAPT. In SKOV3 and IGROV1 cells, the co-stimulation blocked the cadherin switch and the increase in the transcription factors Snail, Slug, Twist and Zeb1 induced by TGF-β...
January 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27888801/common-profiles-of-notch-signaling-differentiate-disease-free-survival-in-luminal-type-a-and-triple-negative-breast-cancer
#19
Magdalena Orzechowska, Dorota Jędroszka, Andrzej K Bednarek
Breast cancer (BC) is characterized by high heterogeneity regarding its biology and clinical characteristics. The Notch pathway regulates such processes as organ modeling and epithelial-to-mesenchymal transition (EMT).The aim of the study was to determine the effect of differential expression of Notch members on disease-free survival (DFS) in luminal type A (lumA) and triple negative (TN) BC.The differential expression of 19 Notch members was examined in a TCGA BC cohort. DFS analysis was performed using the log-rank test (p<0...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27880939/inhibition-of-the-transcriptional-repressor-complex-bcl-6-bcor-induces-endothelial-sprouting-but-does-not-promote-tumor-growth
#20
Elisabeth Buchberger, Dietmar Payrhuber, Miriam El Harchi, Branislav Zagrapan, Katharina Scheuba, Anna Zommer, Edina Bugyik, Balazs Dome, Julia Barbara Kral, Waltraud Cornelia Schrottmaier, Gernot Schabbauer, Peter Petzelbauer, Marion Gröger, Martin Bilban, Christine Brostjan
The oncogenic potential of the transcriptional repressor Bcl-6 (B-cell lymphoma 6) was originally discovered in non-Hodgkin patients and the soluble Bcl-6 inhibitor 79-6 was developed to treat diffuse large B-cell lymphomas with aberrant Bcl-6 expression. Since we found Bcl-6 and its co-repressor BCoR (Bcl-6 interacting co-repressor) to be regulated in human microvascular endothelium by colorectal cancer cells, we investigated their function in sprouting angiogenesis which is central to tumor growth. Based on Bcl-6/BCoR gene silencing we found that the transcriptional repressor complex in fact constitutes an endogenous inhibitor of vascular sprouting by supporting the stalk cell phenotype: control of Notch target genes (HES1, HEY1, DLL4) and cell cycle regulators (cyclin A and B1)...
November 21, 2016: Oncotarget
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