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https://www.readbyqxmd.com/read/28304136/zebrafish-models-of-non-canonical-wnt-planar-cell-polarity-signalling-fishing-for-valuable-insight-into-vertebrate-polarized-cell-behavior
#1
REVIEW
Maria Jussila, Brian Ciruna
Planar cell polarity (PCP) coordinates the uniform orientation, structure and movement of cells within the plane of a tissue or organ system. It is beautifully illustrated in the polarized arrangement of bristles and hairs that project from specialized cell surfaces of the insect abdomen and wings, and pioneering genetic studies using the fruit fly, Drosophila melanogaster, have defined a core signalling network underlying PCP. This core PCP/non-canonical Wnt signalling pathway is evolutionarily conserved, and studies in zebrafish have helped transform our understanding of PCP from a peculiarity of polarized epithelia to a more universal cellular property that orchestrates a diverse suite of polarized cell behaviors that are required for normal vertebrate development...
March 17, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28303901/mutual-reinforcement-between-telomere-capping-and-canonical-wnt-signalling-in-the-intestinal-stem-cell-niche
#2
Ting-Lin B Yang, Qijun Chen, Jennifer T Deng, Geetha Jagannathan, John W Tobias, David C Schultz, Shan Wang, Christopher J Lengner, Anil K Rustgi, John P Lynch, F Brad Johnson
Critical telomere shortening (for example, secondary to partial telomerase deficiency in the rare disease dyskeratosis congenita) causes tissue pathology, but underlying mechanisms are not fully understood. Mice lacking telomerase (for example, mTR(-/-) telomerase RNA template mutants) provide a model for investigating pathogenesis. In such mice, after several generations of telomerase deficiency telomeres shorten to the point of uncapping, causing defects most pronounced in high-turnover tissues including intestinal epithelium...
March 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28299632/transgenic-expression-of-a-canonical-wnt-inhibitor-kallistatin-is-associated-with-decreased-circulating-cd19-b-lymphocytes-in-the-peripheral-blood
#3
Jeffrey D McBride, Xiaochen Liu, William L Berry, Ralf Janknecht, Rui Cheng, Kelu Zhou, Evangelos V Badiavas, Jian-Xing Ma
Members of the family of serine proteinase inhibitors, such as kallistatin, have been shown to inhibit canonical Wnt-TCF/LEF-β-catenin signaling via their interactions with the Wnt co-receptor LRP6. Yet the effects of transgenic overexpression of anti-Wnt serpins on hematopoiesis and lymphopoiesis are not well known. We studied the effects of human kallistatin (SERPINA4) on Wnt reporter activity in various cell types throughout the hematopoietic system and associated impacts on circulating white blood cell profiles...
March 15, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28298922/interactions-between-ppar-gamma-and-the-canonical-wnt-beta-catenin-pathway-in-type-2-diabetes-and-colon-cancer
#4
REVIEW
Yves Lecarpentier, Victor Claes, Alexandre Vallée, Jean-Louis Hébert
In both colon cancer and type 2 diabetes, metabolic changes induced by upregulation of the Wnt/beta-catenin signaling and downregulation of peroxisome proliferator-activated receptor gamma (PPAR gamma) may help account for the frequent association of these two diseases. In both diseases, PPAR gamma is downregulated while the canonical Wnt/beta-catenin pathway is upregulated. In colon cancer, upregulation of the canonical Wnt system induces activation of pyruvate dehydrogenase kinase and deactivation of the pyruvate dehydrogenase complex...
2017: PPAR Research
https://www.readbyqxmd.com/read/28297666/canonical-wnt-signaling-ameliorates-aging-of-intestinal-stem-cells
#5
Kodandaramireddy Nalapareddy, Kalpana J Nattamai, Rupali S Kumar, Rebekah Karns, Kathryn A Wikenheiser-Brokamp, Leesa L Sampson, Maxime M Mahe, Nambirajan Sundaram, Mary-Beth Yacyshyn, Bruce Yacyshyn, Michael A Helmrath, Yi Zheng, Hartmut Geiger
Although intestinal homeostasis is maintained by intestinal stem cells (ISCs), regeneration is impaired upon aging. Here, we first uncover changes in intestinal architecture, cell number, and cell composition upon aging. Second, we identify a decline in the regenerative capacity of ISCs upon aging because of a decline in canonical Wnt signaling in ISCs. Changes in expression of Wnts are found in stem cells themselves and in their niche, including Paneth cells and mesenchyme. Third, reactivating canonical Wnt signaling enhances the function of both murine and human ISCs and, thus, ameliorates aging-associated phenotypes of ISCs in an organoid assay...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28296140/inhibitors-of-stat3-%C3%AE-catenin-and-igf-1r-sensitize%C3%A2-mouse-pik3ca%C3%A2-mutant%C3%A2-breast-cancer-to-pi3k-inhibitors
#6
Vanessa F Merino, Soonweng Cho, Xiaohui Liang, Sunju Park, Kideok Jin, Qian Chen, Duojia Pan, Cynthia A Zahnow, Alan R Rein, Saraswati Sukumar
Although mutations in the phosphoinositide 3-kinase-catalytic subunit (PIK3CA) are common in breast cancer, PI3K inhibitors alone have shown modest efficacy. We sought to identify additional pathways altered in PIK3CA mutant tumors that might be targeted in combination with PI3K inhibitors. We generated two transgenic mouse models expressing the human PIK3CA-H1047R and the -E545K hotspot mutant genes in the mammary gland and evaluated their effects on development and tumor formation. Molecular analysis identified pathways altered in these mutant tumors, which were also targeted in multiple cells lines derived from the PIK3CA tumors...
March 15, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28293067/syndecan-1-acts-as-an-important-regulator-of-cxcl1-expression-and-cellular-interaction-of-human-endometrial-stromal-and-trophoblast-cells
#7
Dunja Maria Baston-Buest, Olga Altergot-Ahmad, Sarah Jean Pour, Jan-Steffen Krüssel, Udo Rudolf Markert, Tanja Natascha Fehm, Alexandra Petra Bielfeld
Successful implantation of the embryo into the human receptive endometrium is substantial for the establishment of a healthy pregnancy. This study focusses on the role of Syndecan-1 at the embryo-maternal interface, the multitasking coreceptor influencing ligand concentration, release and receptor presentation, and cellular morphology. CXC motif ligand 1, being involved in chemotaxis and angiogenesis during implantation, is of special interest as a ligand of Syndecan-1. Human endometrial stromal cells with and without Syndecan-1 knock-down were decidualized and treated with specific inhibitors to evaluate signaling pathways regulating CXC ligand 1 expression...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28293052/beta-catenin-forms-protein-aggregation-at-high-concentrations-in-hek293tcells
#8
Marie Saghaeian Jazi, Seyed Mahmoud Arab Najafi
BACKGROUND: The canonical Wnt signal transduction (or the Wnt/β-catenin pathway) plays a crucial role in the development of animals and in carcinogenesis. Beta-catenin is the central component of this signaling pathway. The activation of Wnt/β-catenin signaling results in the cytoplasmic and nuclear accumulation of β-catenin. In the nucleus, β-catenin interacts with the TCF/LEF transcription factors and, therefore, participates in the upregulation or downregulation of some important genes involved in diverse cellular activities...
January 2017: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/28289266/wnts-synergize-to-activate-%C3%AE-catenin-signaling
#9
Anshula Alok, Zhengdeng Lei, N Suhas Jagannathan, Simran Kaur, Steven G Rozen, Lisa Tucker-Kellogg, David M Virshup
Wnt ligands regulate diverse signaling pathways during development, maintenance of tissue homeostasis, and in various disease states. While signaling regulated by individual Wnts has been extensively studied, Wnts are rarely expressed alone, and the consequences of Wnt gene co-expression are not well understood. We studied the effect of co-expression of Wnts on the β-catenin signaling pathway. While some Wnts are deemed 'non-canonical' due to their limited ability to activate β-catenin when expressed alone, unexpectedly, we find that multiple Wnt combinations can synergistically activate β-catenin signaling in multiple cell types...
March 13, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28288111/gpr124-is-essential-for-blood-brain-barrier-integrity-in-central-nervous-system-disease
#10
Junlei Chang, Michael R Mancuso, Carolina Maier, Xibin Liang, Kanako Yuki, Lu Yang, Jeffrey W Kwong, Jing Wang, Varsha Rao, Mario Vallon, Cynthia Kosinski, J J Haijing Zhang, Amanda T Mah, Lijun Xu, Le Li, Sharareh Gholamin, Teresa F Reyes, Rui Li, Frank Kuhnert, Xiaoyuan Han, Jenny Yuan, Shin-Heng Chiou, Ari D Brettman, Lauren Daly, David C Corney, Samuel H Cheshier, Linda D Shortliffe, Xiwei Wu, Michael Snyder, Pak Chan, Rona G Giffard, Howard Y Chang, Katrin Andreasson, Calvin J Kuo
Although blood-brain barrier (BBB) compromise is central to the etiology of diverse central nervous system (CNS) disorders, endothelial receptor proteins that control BBB function are poorly defined. The endothelial G-protein-coupled receptor (GPCR) Gpr124 has been reported to be required for normal forebrain angiogenesis and BBB function in mouse embryos, but the role of this receptor in adult animals is unknown. Here Gpr124 conditional knockout (CKO) in the endothelia of adult mice did not affect homeostatic BBB integrity, but resulted in BBB disruption and microvascular hemorrhage in mouse models of both ischemic stroke and glioblastoma, accompanied by reduced cerebrovascular canonical Wnt-β-catenin signaling...
March 13, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28287244/functional-differences-between-tcf1-isoforms-in-early-xenopus-development
#11
Giulietta Roël, Olaf Van Den Broek, Olivier Destrée
In Xenopus gastrula stage embryos, four isoforms of Tcf1 (B, C, D and E) are present with high amino acid sequence conservation compared to fish, mice and human. We studied possible functional differences between these Tcf1 isoforms during early Xenopus development. After overexpression of single Tcf1 isoforms, two distinct phenotypes were observed. Overexpression of the B or D isoforms of Tcf1, which both lack a C-clamp, enhances early canonical Wnt signaling and induces ectopic dorsal mesoderm at the expense of ventrolateral mesoderm prior to gastrulation, causing severe antero-dorzalization of embryos...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28280366/salinomycin-repressed-the-epithelial-mesenchymal-transition-of-epithelial-ovarian-cancer-cells-via-downregulating-wnt-%C3%AE-catenin-pathway
#12
Rui Li, Taotao Dong, Chen Hu, Jingjing Lu, Jun Dai, Peishu Liu
Epithelial ovarian cancer (EOC) is the leading cause of death among all gynecological malignancies. Most patients are diagnosed in the advanced stage and have distant metastasis ultimately. Salinomycin has been demonstrated to reduce invasive capacity of multiple tumor cells. The objective of this study was to investigate the effects of salinomycin on EOC cells. The cell counting kit 8 (CCK-8) and Boyden chamber assays showed that salinomycin could effectively reduce the abilities of proliferation, migration and invasion in EOC cells...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28276699/p120-catenin-in-canonical-wnt-signaling
#13
Mireia Duñach, Beatriz Del Valle-Pérez, Antonio García de Herreros
Canonical Wnt signaling controls β-catenin protein stabilization, its translocation to the nucleus and the activation of β-catenin/Tcf-4-dependent transcription. In this review, we revise and discuss the recent results describing actions of p120-catenin in different phases of this pathway. More specifically, we comment its involvement in four different steps: (i) the very early activation of CK1ɛ, essential for Dvl-2 binding to the Wnt receptor complex; (ii) the internalization of GSK3 and Axin into multivesicular bodies, necessary for a complete stabilization of β-catenin; (iii) the activation of Rac1 small GTPase, required for β-catenin translocation to the nucleus; and (iv) the release of the inhibitory action caused by Kaiso transcriptional repressor...
March 3, 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28273449/r-spondin1-controls-muscle-cell-fusion-through-dual-regulation-of-antagonistic-wnt-signaling-pathways
#14
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/28270600/diverse-regulation-of-mammary-epithelial-growth-and-branching-morphogenesis-through-noncanonical-wnt-signaling
#15
Kai Kessenbrock, Prestina Smith, Sander Christiaan Steenbeek, Nicholas Pervolarakis, Raj Kumar, Yasuhiro Minami, Andrei Goga, Lindsay Hinck, Zena Werb
The mammary gland consists of an adipose tissue that, in a process called branching morphogenesis, is invaded by a ductal epithelial network comprising basal and luminal epithelial cells. Stem and progenitor cells drive mammary growth, and their proliferation is regulated by multiple extracellular cues. One of the key regulatory pathways for these cells is the β-catenin-dependent, canonical wingless-type MMTV integration site family (WNT) signaling pathway; however, the role of noncanonical WNT signaling within the mammary stem/progenitor system remains elusive...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28267592/sfrp4-signalling-of-apoptosis-and-angiostasis-uses-nitric-oxide-cgmp-permeability-axis-of-endothelium
#16
Uttara Saran, Mani Krishna Priya, Uma Maheswari Balaguru, Akila Swaminathan, Shunmugam Nagarajan, Arun Dharmarajan, Suvro Chatterjee
Nitric oxide (NO) plays a critical role in endothelial functions such as cellular migration, vascular permeability and angiogenesis. Angiogenesis, the formation of new blood vessels from "pre-existing" ones is a carefully regulated process and essential during reproduction, development and wound healing. Previously our lab group reported that Secreted Frizzled-Related Protein 4 (sFRP4) could inhibit angiogenesis in both in vitro and in vivo conditions. sFRP4 belongs to a family of secreted glycoproteins that function as antagonists of the canonical Wnt signalling pathway...
March 3, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28259909/prostate-apoptosis-response-4-par4-expression-modulates-wnt-signaling-pathways-in-mcf7-breast-cancer-cells-a-possible-mechanism-underlying-par4-mediated-docetaxel-chemosensitivity
#17
Simone Aparecida de Bessa Garcia, Ana Carolina Pavanelli, Natália Cruz E Melo, Maria Aparecida Nagai
Docetaxel is an effective drug for the treatment of metastatic breast cancer. However, the exact mechanisms and/or markers associated with chemosensitivity or resistance to docetaxel remain unclear. We previously showed that the expression of prostate apoptosis response 4 (PAR4) inhibits the growth of MCF7 breast cancer cells and increases their sensitivity to docetaxel. Using cDNA microarray analysis, we evaluated transcriptome changes in MCF7 cells expressing increased levels of PAR4 and control cells before and after docetaxel treatment...
February 21, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28259801/effect-of-tetrahedral-dna-nanostructures-on-osteogenic-differentiation-of-mesenchymal-stem-cells-via-activation-of-the-wnt-%C3%AE-catenin-signaling-pathway
#18
Xiao-Ru Shao, Shi-Yu Lin, Qiang Peng, Si-Rong Shi, Xiao-Long Li, Tao Zhang, Yun-Feng Lin
Adipose-derived stem cells (ADSCs) are considered to be ideal stem cell sources for bone regeneration owing to their ability to differentiate into osteo-like cells. Therefore, they have attracted increasing attention in recent years. Tetrahedral DNA nanostructures (TDNs), a new type of DNA-based biomaterials, have shown great potential for biomedical applications. In the present work, we aimed to investigate the role played by TDNs in osteogenic differentiation and proliferation of ADSCs and tried to explore if the canonical Wnt signal pathway could be the vital biological mechanism driving these cellular responses...
March 1, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28253399/foxc1-and-foxc2-in-the-neural-crest-are-required-for-ocular-anterior-segment-development
#19
Seungwoon Seo, Lisheng Chen, Wenzhong Liu, Demin Zhao, Kathryn M Schultz, Amy Sasman, Ting Liu, Hao F Zhang, Philip J Gage, Tsutomu Kume
Purpose: The large Forkhead (Fox) transcription factor family has essential roles in development, and mutations cause a wide range of ocular and nonocular disease. One member, Foxc2 is expressed in neural crest (NC)-derived periocular mesenchymal cells of the developing murine eye; however, its precise role in the development, establishment, and maintenance of the ocular surface has yet to be investigated. Methods: To specifically delete Foxc2 from NC-derived cells, conditional knockout mice for Foxc2 (NC-Foxc2-/-) were generated by crossing Foxc2F mice with Wnt1-Cre mice...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28251982/-3d-structure-of-dkk1-indicates-its-involvement-in-both-canonical-and-non-canonical-wnt-pathways
#20
S Khalili, M J Rasaee, T Bamdad
Dikkoppf-1 (DKK1) is an antagonist of the canonical Wnt signaling pathway. The importance of DKK1 as a diagnostic and therapeutic agent in a wide range of diseases along with its significance in a variety of biological processes accentuate the necessity to decipher its 3D structure that would pave the way towards the development of relevant selective inhibitors. A DKK1 structure model predicted by the Robetta server with structural refinements including a 10 ns molecular dynamics run was subjected to functional and docking analyses...
January 2017: Molekuliarnaia Biologiia
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