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https://www.readbyqxmd.com/read/28813421/stromal-r-spondin-orchestrates-gastric-epithelial-stem-cells-and-gland-homeostasis
#1
Michael Sigal, Catriona Y Logan, Marta Kapalczynska, Hans-Joachim Mollenkopf, Hilmar Berger, Bertram Wiedenmann, Roeland Nusse, Manuel R Amieva, Thomas F Meyer
The constant regeneration of stomach epithelium is driven by long-lived stem cells, but the mechanism that regulates their turnover is not well understood. We have recently found that the gastric pathogen Helicobacter pylori can activate gastric stem cells and increase epithelial turnover, while Wnt signalling is known to be important for stem cell identity and epithelial regeneration in several tissues. Here we find that antral Wnt signalling, marked by the classic Wnt target gene Axin2, is limited to the base and lower isthmus of gastric glands, where the stem cells reside...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28739799/lgr5-receptor-promotes-cell-cell-adhesion-in-stem-cells-and-colon-cancer-cells-via-the-iqgap1-rac1-pathway
#2
Kendra S Carmon, Xing Gong, Jing Yi, Ling Wu, Anthony Thomas, Catherine M Moore, Ikuo Masuho, David J Timson, Kirill A Martemyanov, Qingyun J Liu
Leucine rich repeat containing G protein coupled receptor 5 (LGR5) is a bona fide marker of adult stem cells in several epithelial tissues, most notably in the intestinal crypts and is highly upregulated in many colorectal, hepatocellular, and ovarian cancers. LGR5 activation by R-spondin (RSPO) ligands potentiates Wnt/β-catenin signaling in vitro, yet deletion of LGR5 in stem cells has little or no effect on Wnt/β-catenin signaling or cell proliferation in vivo. Remarkably, modulation of LGR5 expression has a major impact on the actin cytoskeletal structure and cell adhesion in the absence of RSPO stimulation, but the molecular mechanism is unclear...
July 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28695896/r-spondin-chromosome-rearrangements-drive-wnt-dependent-tumour-initiation-and-maintenance-in-the-intestine
#3
Teng Han, Emma M Schatoff, Charles Murphy, Maria Paz Zafra, John E Wilkinson, Olivier Elemento, Lukas E Dow
Defining the genetic drivers of cancer progression is a key in understanding disease biology and developing effective targeted therapies. Chromosome rearrangements are a common feature of human malignancies, but whether they represent bona fide cancer drivers and therapeutically actionable targets, requires functional testing. Here, we describe the generation of transgenic, inducible CRISPR-based mouse systems to engineer and study recurrent colon cancer-associated EIF3E-RSPO2 and PTPRK-RSPO3 chromosome rearrangements in vivo...
July 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28661485/osteoblastic-heparan-sulfate-glycosaminoglycans-control-bone-remodeling-by-regulating-wnt-signaling-and-the-crosstalk-between-bone-surface-and-marrow-cells
#4
Rafik Mansouri, Yohann Jouan, Eric Hay, Claudine Blin-Wakkach, Monique Frain, Agnès Ostertag, Carole Le Henaff, Caroline Marty, Valérie Geoffroy, Pierre J Marie, Martine Cohen-Solal, Dominique Modrowski
Stimulating bone formation is an important challenge for bone anabolism in osteoporotic patients or to repair bone defects. The osteogenic properties of matrix glycosaminoglycans (GAGs) have been explored; however, the functions of GAGs at the surface of bone-forming cells are less documented. Syndecan-2 is a membrane heparan sulfate proteoglycan that is associated with osteoblastic differentiation. We used a transgenic mouse model with high syndecan-2 expression in osteoblasts to enrich the bone surface with cellular GAGs...
June 29, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28651234/microrna-493-suppresses-hepatocellular-carcinoma-tumorigenesis-through-down-regulation-of-anthrax-toxin-receptor-1-antxr1-and-r-spondin-2-rspo2
#5
Yuqiang Xu, Kuikui Ge, Junhao Lu, Jinjiang Huang, Wei Wei, Qingshan Huang
Hepatocellular carcinoma (HCC) is known as a highly prevalent cancer with a poor prognosis and short survival time, despite intensive research and clinical efforts. Increasing numbers of studies have reported that microRNAs are involved in the malignant behavior of hepatocellular carcinoma cells via directly targeting multiple oncogenes or tumor suppressors. Here, we report that the expression of microRNA-493 (miR-493) is decreased in HCC cell lines and in tumor tissues. Overexpression of miR-493 in HCC cells dramatically inhibited cell proliferation and colony-formation in vitro and inhibited tumor formation of HCC cell xenografts in vivo...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28642339/establishment-of-a-novel-three-dimensional-primary-culture-model-for-hippocampal-neurogenesis
#6
Tatsuya Usui, Masashi Sakurai, Hideyoshi Kawasaki, Takashi Ohama, Hideyuki Yamawaki, Koichi Sato
New neurons are generated in the adult hippocampus throughout life and contribute to the functions of learning and memory. Nevertheless, the mechanisms by which disrupted neurogenesis regulates central nervous system (CNS) disorders are not fully understood. Here, we established a novel 3D culture system of hippocampal neurogenesis using air liquid interface (ALI) culture and Matrigel culture from mouse hippocampus tissues. After isolated mouse hippocampus tissue fragments were seeded into ALI wells and cultured in stemness-stimulated media containing Wnt, EGF, Noggin and R-spondin for 7 days, small spheres gradually appeared in the tissues...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28626093/-expression-of-regulatory-factor-r-spondin-family-in-%C3%A2-wnt-signaling-pathway-in-colorectal-cancer-and-%C3%A2-its-clinical-significance
#7
Heli Liu, Yuan Zhou, Fengbo Tan, Yinan Wang, Haiping Pei
To explore the expression of R-spondin family in colorectal cancer tissues and adjacent tissues, and to evaluate its relationship with clinic-pathological stage.
 Methods: A total of 64 samples of colorectal cancer tissues and adjacent tissues were collected from the patients, who received radical surgery in Xiangya Hospital, Central South University between January 2014 and August 2014. The mRNA and protein expression levels of R-spondin 1-4 and β-catenin in the colorectal cancer tissues and adjacent tissues were detected by qRT-PCR and immunohistochemistry...
May 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28623072/commentary-on-integrative-clinical-genomics-of-advanced-prostate-cancer-robinson-d-van-allen-em-wu-ym-schultz-n-lonigro-rj-mosquera-jm-montgomery-b-taplin-me-pritchard-cc-attard-g-beltran-h-abida-w-bradley-rk-vinson-j-cao-x-vats-p-kunju-lp-hussain-m-feng-fy
#8
Stephen J Freedland, William J Aronson
Toward development of a precision medicine framework for metastatic, castration-resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole-exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53, and PTEN were frequent (40%-60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified new genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin, and ZBTB16/PLZF...
June 13, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28600110/rspo2-suppresses-colorectal-cancer-metastasis-by-counteracting-the-wnt5a-fzd7-driven-noncanonical-wnt-pathway
#9
Xiaoming Dong, Wanqin Liao, Li Zhang, Xi Tu, Jin Hu, Tianke Chen, Xiaowei Dai, Yan Xiong, Weicheng Liang, Chaodong Ding, Rui Liu, Juji Dai, Ouchen Wang, Liting Lu, Xincheng Lu
R-spondins play critical roles in development, stem cell survival, and tumorigenicity by modulating Wnt/β-catenin signaling; however, the role of R-spondins in noncanonical Wnt signaling regulation remains largely unknown. We demonstrate here that R-spondin 2 (RSPO2) has an inhibitory effect on colorectal cancer (CRC) cell migration, invasion, and metastasis. Reduced RSPO2 expression was associated with tumor metastasis and poor survival in CRC patients. The metastasis-suppressive activity of RSPO2 was independent of the Wnt/β-catenin signaling pathway but dependent on the Fzd7-mediated noncanonical Wnt signaling pathway...
June 6, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28586642/r-spondin-is-more-than-just-wnt-s-sidekick
#10
David J Huels, Owen J Sansom
The intestinal crypt and its stem cells are dependent on the Wnt pathway. Reporting in Nature, Yan et al. (2017) show that Wnts and Wnt signaling potentiator R-spondins have non-interchangeable roles. Both are necessary for intestinal stem cell (ISC) maintenance, and R-spondins are the limiting factor that defines ISC number.
June 5, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28512242/a-systematic-analysis-of-oncogenic-gene-fusions-in-primary-colon-cancer
#11
Wigard P Kloosterman, Robert R J Coebergh van den Braak, Mark Pieterse, Markus J van Roosmalen, Anieta M Sieuwerts, Christina Stangl, Ronne Brunekreef, Zarina S Lalmahomed, Salo Ooft, Anne van Galen, Marcel Smid, Armel Lefebvre, Fried Zwartkruis, John W M Martens, John A Foekens, Katharina Biermann, Marco J Koudijs, Jan N M Ijzermans, Emile E Voest
Genomic rearrangements that give rise to oncogenic gene fusions can offer actionable targets for cancer therapy. Here we present a systematic analysis of oncogenic gene fusions among a clinically well-characterized, prospectively collected set of 278 primary colon cancers spanning diverse tumor stages and clinical outcomes. Gene fusions and somatic genetic variations were identified in fresh frozen clinical specimens by Illumina RNA-sequencing, the STAR fusion gene detection pipeline, and GATK RNA-seq variant calling...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28472820/clinical-value-of-r-spondins-in-triple-negative-and-metaplastic-breast-cancers
#12
F Coussy, F Lallemand, S Vacher, A Schnitzler, W Chemlali, M Caly, A Nicolas, S Richon, D Meseure, R El Botty, L De-Plater, L Fuhrmann, T Dubois, S Roman-Roman, V Dangles-Marie, E Marangoni, I Bièche
BACKGROUND: RSPO ligands, activators of the Wnt/β-catenin pathway, are overexpressed in different cancers. The objective of this study was to investigate the role of RSPOs in breast cancer (BC). METHODS: Expression of RSPO and markers of various cancer pathways were measured in breast tumours and cell lines by qRT-PCR. The effect of RSPO on the Wnt/β-catenin pathway activity was determined by luciferase assay, western blotting, and qRT-PCR. The effect of RSPO2 inhibition on proliferation was determined by using RSPO2 siRNAs...
June 6, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28467820/non-equivalence-of-wnt-and-r-spondin-ligands-during-lgr5-intestinal-stem-cell-self-renewal
#13
Kelley S Yan, Claudia Y Janda, Junlei Chang, Grace X Y Zheng, Kathryn A Larkin, Vincent C Luca, Luis A Chia, Amanda T Mah, Arnold Han, Jessica M Terry, Akifumi Ootani, Kelly Roelf, Mark Lee, Jenny Yuan, Xiao Li, Christopher R Bolen, Julie Wilhelmy, Paige S Davies, Hiroo Ueno, Richard J von Furstenberg, Phillip Belgrader, Solongo B Ziraldo, Heather Ordonez, Susan J Henning, Melissa H Wong, Michael P Snyder, Irving L Weissman, Aaron J Hsueh, Tarjei S Mikkelsen, K Christopher Garcia, Calvin J Kuo
The canonical Wnt/β-catenin signalling pathway governs diverse developmental, homeostatic and pathological processes. Palmitoylated Wnt ligands engage cell-surface frizzled (FZD) receptors and LRP5 and LRP6 co-receptors, enabling β-catenin nuclear translocation and TCF/LEF-dependent gene transactivation. Mutations in Wnt downstream signalling components have revealed diverse functions thought to be carried out by Wnt ligands themselves. However, redundancy between the 19 mammalian Wnt proteins and 10 FZD receptors and Wnt hydrophobicity have made it difficult to attribute these functions directly to Wnt ligands...
May 11, 2017: Nature
https://www.readbyqxmd.com/read/28462013/stromal-progenitor-cells-in-mitigation-of-non-hematopoietic-radiation-injuries
#14
Shilpa Kulkarni, Timothy C Wang, Chandan Guha
PURPOSE OF REVIEW: Therapeutic exposure to high doses of radiation can severely impair organ function due to ablation of stem cells. Normal tissue injury is a dose-limiting toxicity for radiation therapy (RT). Although advances in the delivery of high precision conformal RT has increased normal tissue sparing, mitigating and therapeutic strategies that could alleviate early and chronic radiation effects are urgently needed in order to deliver curative doses of RT, especially in abdominal, pelvic and thoracic malignancies...
December 2016: Current Pathobiology Reports
https://www.readbyqxmd.com/read/28441759/synaptic-homeostasis-and-its-immunological-disturbance-in-neuromuscular-junction-disorders
#15
REVIEW
Masaharu Takamori
In the neuromuscular junction, postsynaptic nicotinic acetylcholine receptor (nAChR) clustering, trans-synaptic communication and synaptic stabilization are modulated by the molecular mechanisms underlying synaptic plasticity. The synaptic functions are based presynaptically on the active zone architecture, synaptic vesicle proteins, Ca(2+) channels and synaptic vesicle recycling. Postsynaptically, they are based on rapsyn-anchored nAChR clusters, localized sensitivity to ACh, and synaptic stabilization via linkage to the extracellular matrix so as to be precisely opposed to the nerve terminal...
April 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28380527/modulation-of-intestinal-cell-differentiation-in-growing-pigs-is-dependent-on-the-fiber-source-in-the-diet
#16
M Saqui-Salces, Z Huang, M Ferrandis Vila, J Li, J A Mielke, P E Urriola, G C Shurson
Feeding high-fiber diets decreases cost, but also caloric and nutritional efficiency by modifying intestinal morphology and function. We analyzed the changes in intestinal cell composition, nutrient transporters and receptors, and cell differentiation induced by fibers from different sources. Forty-six finishing pigs (BW 84 ± 7 kg) were fed 1 of 4 diets: corn-soybean (Control; = 12), 23% wheat straw (WS; = 11), 55% corn distillers dried grains with solubles (DDGS; = 11), and 30% soybean hulls (SBH; = 12). Pigs were fed 2 meals daily to an amount equivalent to 2...
March 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28347989/wrn-conditioned-media-is-sufficient-for-in-vitro-propagation-of-intestinal-organoids-from-large-farm-and-small-companion-animals
#17
Robin H Powell, Michael S Behnke
Recent years have seen significant developments in the ability to continuously propagate organoids derived from intestinal crypts. These advancements have been applied to mouse and human samples providing models for gastrointestinal tissue development and disease. We adapt these methods for the propagation of intestinal organoids (enteroids) from various large farm and small companion (LF/SC) animals, including cat, dog, cow, horse, pig, sheep and chicken. We show that LF/SC enteroids propagate and expand in L-WRN conditioned media containing signaling factors Wnt3a, R-spondin-3, and Noggin (WRN)...
May 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28334609/basolateral-to-central-amygdala-neural-circuits-for-appetitive-behaviors
#18
Joshua Kim, Xiangyu Zhang, Shruti Muralidhar, Sarah A LeBlanc, Susumu Tonegawa
Basolateral amygdala (BLA) principal cells are capable of driving and antagonizing behaviors of opposing valence. BLA neurons project to the central amygdala (CeA), which also participates in negative and positive behaviors. However, the CeA has primarily been studied as the site for negative behaviors, and the causal role for CeA circuits underlying appetitive behaviors is poorly understood. Here, we identify several genetically distinct populations of CeA neurons that mediate appetitive behaviors and dissect the BLA-to-CeA circuit for appetitive behaviors...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28273449/r-spondin1-controls-muscle-cell-fusion-through-dual-regulation-of-antagonistic-wnt-signaling-pathways
#19
Floriane Lacour, Elsa Vezin, C Florian Bentzinger, Marie-Claude Sincennes, Lorenzo Giordani, Arnaud Ferry, Robert Mitchell, Ketan Patel, Michael A Rudnicki, Marie-Christine Chaboissier, Anne-Amandine Chassot, Fabien Le Grand
Wnt-mediated signals are involved in many important steps in mammalian regeneration. In multiple cell types, the R-spondin (Rspo) family of secreted proteins potently activates the canonical Wnt/β-catenin pathway. Here, we identify Rspo1 as a mediator of skeletal muscle tissue repair. First, we show that deletion of Rspo1 results in global alteration of muscle regeneration kinetics following acute injury. We find that muscle progenitor cells lacking Rspo1 show delayed differentiation due to reduced activation of Wnt/β-catenin target genes...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28272338/evidence-of-the-role-of-r-spondin-1-and-its-receptor-lgr4-in-the-transmission-of-mechanical-stimuli-to-biological-signals-for-bone-formation
#20
Gui-Xun Shi, Xin-Feng Zheng, Chao Zhu, Bo Li, Yu-Ren Wang, Sheng-Dan Jiang, Lei-Sheng Jiang
The bone can adjust its mass and architecture to mechanical stimuli via a series of molecular cascades, which have been not yet fully elucidated. Emerging evidence indicated that R-spondins (Rspos), a family of secreted agonists of the Wnt/β-catenin signaling pathway, had important roles in osteoblastic differentiation and bone formation. However, the role of Rspo proteins in mechanical loading-influenced bone metabolism has never been investigated. In this study, we found that Rspo1 was a mechanosensitive protein for bone formation...
March 7, 2017: International Journal of Molecular Sciences
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