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https://www.readbyqxmd.com/read/28548684/origins-of-anterior-posterior-polarity-by-localized-activation-of-disheveled
#1
Jeff Chieh-Fu Peng, Lingyu Wang, Athula H Wikramanayake
Most animal eggs have a primordial polarity, termed the animal-vegetal (AV) axis, that frequently predicts the anterior-posterior (AP) axis of the embryo and adult. Transformation of the AV polarity of the egg to the AP polarity of the embryo in many species is mediated by the localized activation of canonical Wnt (cWnt) signaling in vegetal blastomeres by maternal determinants. In the sea urchin egg, cWnt signal transduction is facilitated by localized "activation" of the Disheveled protein, a central regulator of Wnt signaling...
May 26, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28545982/canonical-wnt-signaling-in-diabetic-retinopathy
#2
Qian Chen, Jian-Xing Ma
Diabetic retinopathy (DR) is a common eye complication of diabetes, and the pathogenic mechanism of DR is still under investigation. The canonical Wnt signaling pathway is an evolutionarily conserved pathway that plays fundamental roles in embryogenesis and adult tissue homeostasis. Wnt signaling regulates expression of multiple genes that control retinal development and eye organogenesis, and dysregulated Wnt signaling plays pathophysiological roles in many ocular diseases, including DR. This review highlights recent progress in studies of Wnt signaling in DR...
May 22, 2017: Vision Research
https://www.readbyqxmd.com/read/28539358/protein-kinase-c-%C3%AE%C2%B5-stabilizes-%C3%AE-catenin-and-regulates-its-subcellular-localization-in-podocytes
#3
Michelle Duong, Xuejiao Yu, Beina Teng, Patricia Schroder, Hermann Haller, Susanne Eschenburg, Mario Schiffer
Kidney disease has been linked to dysregulated signaling via protein kinase C (PKC) in kidney cells such as podocytes. PKCα is a conventional isoform of PKC and a well-known binding partner of β-catenin, which promotes its degradation. β-Catenin is the main effector of the canonical Wnt pathway and is critical in cell adhesion. However, whether other PKC isoforms interact with β-catenin has not been studied systematically. Here we demonstrate that PKCε-deficient mice, which develop proteinuria and glomerulosclerosis, display a lower β-catenin expression compared to PKC wildtype mice, consistent with an altered phenotype of podocytes in culture...
May 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28534995/low%C3%A2-level-mechanical-vibration-enhances-osteoblastogenesis-via-a-canonical-wnt-signaling%C3%A2-associated-mechanism
#4
Heqi Gao, Mingming Zhai, Pan Wang, Xuhui Zhang, Jing Cai, Xiaofei Chen, Guanghao Shen, Erping Luo, Da Jing
Osteoporosis is a skeletal metabolic disease characterized by reduced bone mass and a high susceptibility to fractures, in which osteoblasts and osteoclasts are highly involved in the abnormal bone remodeling processes. Recently, low‑magnitude, high‑frequency whole‑body vibration has been demonstrated to significantly reduce osteopenia experimentally and clinically. However, the underlying mechanism regarding how osteoblastic activity is altered when bone tissues adapt to mechanical vibration remains elusive...
May 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28533765/leptin-induces-mitosis-and-activates-the-canonical-wnt-%C3%AE-catenin-signaling-pathway-in-neurogenic-regions-of-xenopus-tadpole-brain
#5
Melissa Cui Bender, Christopher J Sifuentes, Robert J Denver
In addition to its well-known role as an adipostat in adult mammals, leptin has diverse physiological and developmental actions in vertebrates. Leptin has been shown to promote development of hypothalamic circuits and to induce mitosis in different brain areas of mammals. We investigated the ontogeny of leptin mRNA, leptin actions on cell proliferation in the brain, and gene expression in the preoptic area/hypothalamus of tadpoles of Xenopus laevis. The level of leptin mRNA was low in premetamorphic tadpoles, but increased strongly at the beginning of metamorphosis and peaked at metamorphic climax...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28529724/recent-advances-in-the-management-of-osteoporosis
#6
REVIEW
Seiji Fukumoto, Toshio Matsumoto
There has been substantial progress in the management of patients with osteoporosis and the prevention of osteoporotic fractures. Currently available strong anti-resorptive agents are bisphosphonates and an anti-receptor activator of nuclear factor-kappa B ligand (RANKL) antibody, denosumab. Although bisphosphonates and denosumab both inhibit bone resorption and prevent vertebral and non-vertebral fractures, their mechanisms of action are different. Whereas bisphosphonates' effects on bone mineral density and fracture peak around 3 to 5 years and become plateaued, those of denosumab are maintained for up to 10 years...
2017: F1000Research
https://www.readbyqxmd.com/read/28529629/the-antihelminthic-drug-niclosamide-effectively-inhibits-the-malignant-phenotypes-of-uveal-melanoma-in-vitro-and-in-vivo
#7
Jingfeng Zhou, Bei Jin, Yanli Jin, Yizhi Liu, Jingxuan Pan
Uveal melanoma (UM) is a lethal intraocular malignancy with an average survival of only 2~8 months in patients with hepatic metastasis. Currently, there is no effective therapy for metastatic UM. Here, we reported that niclosamide, an effective repellence of tapeworm that has been approved for use in patients for approximately 50 years, exhibited strong antitumor activity in UM cells in vitro and in vivo. We showed that niclosamide potently inhibited UM cell proliferation, induced apoptosis and reduced migration and invasion...
2017: Theranostics
https://www.readbyqxmd.com/read/28526587/wnt-%C3%AE-catenin-signaling-in-adult-mammalian-epithelial-stem-cells
#8
REVIEW
Kai Kretzschmar, Hans Clevers
Adult stem cells self-renew and replenish differentiated cells in various organs and tissues throughout a mammal's life. Over the last 25 years an ever-growing body of knowledge has unraveled the essential regulation of adult mammalian epithelia by the canonical Wnt signaling with its key intracellular effector β-catenin. In this review, we discuss the principles of the signaling pathway and its role in adult epithelial stem cells of the intestine and skin during homeostasis and tumorigenesis. We further highlight the research that led to the identification of new stem cell markers and methods to study adult stem cells ex vivo...
May 16, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28523736/hyper-activation-of-%C3%AE-catenin-signalling-induced-by-ikk%C3%AE%C2%B5-inhibition-thwarts-colorectal-cancer-cell-proliferation
#9
Jie Chen, Jun Zhao, Xuan Chen, Chengming Ding, Katie Lee, Zeming Jia, Yaoting Zhang, Yuzheng Zhou, Chaoying Wei, Jiantai He, Zanxian Xia, Jian Peng
OBJECTIVE: Aberrant activation of Wnt/β-catenin signalling contributes significantly to the development of human colorectal cancers and β-catenin is the key signalling molecule transducing canonical Wnt/β-catenin signalling. Therefore, β-catenin is a promising therapeutic target for cancer treatment. This study demonstrates that the oncogenic IKKε kinase phosphorylates β-catenin to restrain its hyper activation, therefore promoting colorectal cancer (CRC) cell proliferation. MATERIALS AND METHODS: IKKε and β-catenin expression levels in human colorectal cancer tissues and cell lines were analysed by immunohistochemical staining and Western blotting...
May 19, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28523267/a-novel-role-for-the-bmp-antagonist-noggin-in-sensitizing-cells-to-non-canonical-wnt-5a-ror2-disheveled-pathway-activation
#10
Ondrej Bernatik, Tomasz Radaszkiewicz, Martin Behal, Zankruti Dave, Florian Witte, Annika Mahl, Nicole H Cernohorsky, Pavel Krejci, Sigmar Stricker, Vitezslav Bryja
Mammalian limb development is driven by the integrative input from several signaling pathways; a failure to receive or a misinterpretation of these signals results in skeletal defects. The brachydactylies, a group of overlapping inherited human hand malformation syndromes, are mainly caused by mutations in BMP signaling pathway components. Two closely related forms, Brachydactyly type B2 (BDB2) and BDB1 are caused by mutations in the BMP antagonist Noggin (NOG) and the atypical receptor tyrosine kinase ROR2 that acts as a receptor in the non-canonical Wnt pathway...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28521150/the-effects-of-copper-oxide-nanoparticles-on-dorsoventral-patterning-convergent-extension-and-neural-and-cardiac-development-of-zebrafish
#11
Jia Xu, Qiuping Zhang, Xu Li, Sihui Zhan, Lifeng Wang, Dongyan Chen
Currently, nanoparticles are widely used in biomedicine and industry. CuO nanoparticles (CuO-NPs) are versatile materials in our daily life and their toxicity has drawn extensive attention. In this study, we concentrate on the effect of CuO-NPs on early zebrafish development. The results reveal that CuO-NPs can induce abnormal phenotypes of a smaller head and eyes and delayed epiboly. The gene expression pattern shows that CuO-NPs spatially narrow the expression of dorsal genes chordin and goosecoid and alter the expression of dlx3, ntl and hgg which are related to the cell migration of gastrulation...
May 4, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28520221/rap1b-is-an-effector-of-axin2-regulating-crosstalk-of-signaling-pathways-during-skeletal-development
#12
Takamitsu Maruyama, Ming Jiang, Alycia Abbott, H-M Ivy Yu, Qirong Huang, Magdalena Chrzanowska-Wodnicka, Emily I Chen, Wei Hsu
Recent identification and isolation of suture stem cells capable of long term self-renewal, clonal expanding and differentiating demonstrate their essential role in calvarial bone development, homeostasis and injury repair. These bona fide stem cells express high level of Axin2 and are able to mediate bone regeneration and repair in a cell autonomous fashion. The importance of Axin2 is further demonstrated by its genetic inactivation in mice causing skeletal deformities resembling craniosynostosis in humans...
May 18, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28506989/fgf-signaling-refines-wnt-gradients-to-regulate-patterning-of-taste-papillae
#13
Michaela Prochazkova, Teemu J Häkkinen, Jan Prochazka, Frantisek Spoutil, Andrew H Jheon, Youngwook Ahn, Robb Krumlauf, Jukka Jernvall, Ophir D Klein
The patterning of repeated structures is a major theme in developmental biology, and the interrelationship between spacing and size of such structures is an open question. Fungiform papillae are repeated epithelial structures that house taste buds on the anterior tongue. Here, we report that FGF signaling is a critical regulator of fungiform papillae development. We found that mesenchymal FGF10 controls the size of the papillary area, while overall patterning remains unchanged. Our results show that FGF signaling negatively affects the extent of canonical Wnt signaling, which is the main activation pathway during fungiform papillae development, but this effect does not occur at the level of gene transcription...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28503404/wnt-signaling-in-normal-and-malignant-stem-cells
#14
Dheeraj Bhavanasi, Peter S Klein
Wnt signaling plays important roles in stem cell self-renewal and differentiation in adults as well as in embryonic development. Mutations that activate canonical Wnt/β-catenin signaling also initiate and maintain several cancer states, including colorectal cancer and leukemia, and hence Wnt inhibitors are currently being explored as therapeutic options. In this review, we summarize previous studies and update recent findings on canonical Wnt signaling and its components, as well as their roles in somatic stem cell homeostasis and maintenance of cancer initiating cells...
December 2016: Current Stem Cell Reports
https://www.readbyqxmd.com/read/28501624/autophagy-is-essential-for-the-differentiation-of-porcine-pscs-into-insulin-producing-cells
#15
Lipeng Ren, Hong Yang, Yanhua Cui, Shuanshuan Xu, Fen Sun, Na Tian, Jinlian Hua, Sha Peng
Porcine pancreatic stem cells (PSCs) are seed cells with potential use for diabetes treatment. Stem cell differentiation requires strict control of protein turnover and lysosomal digestion of organelles. Autophagy is a highly conserved process that controls the turnover of organelles and proteins within cells and contributes to the balance of cellular components. However, whether autophagy plays roles in PSC differentiation remains unknown. In this study, we successfully induced porcine PSCs into insulin-producing cells and found that autophagy was activated during the second induction stage...
May 10, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28501501/anti-tumor-effects-of-differentiation-inducing-factor-1-in-malignant-melanoma-gsk-3-mediated-inhibition-of-cell-proliferation-and-gsk-3-independent-suppression-of-cell-migration-and-invasion
#16
Masaki Arioka, Fumi Takahashi-Yanaga, Momoko Kubo, Kazunobu Igawa, Katsuhiko Tomooka, Toshiyuki Sasaguri
Differentiation-inducing factor-1 (DIF-1) isolated from Dictyostelium discoideum strongly inhibits the proliferation of various mammalian cells through the activation of glycogen synthase kinase-3 (GSK-3). To evaluate DIF-1 as a novel anti-cancer agent for malignant melanoma, we examined whether DIF-1 has anti-proliferative, anti-migratory, and anti-invasive effects on melanoma cells using in vitro and in vivo systems. DIF-1 reduced the expression levels of cyclin D1 and c-Myc by facilitating their degradation via GSK-3 in mouse (B16BL6) and human (A2058) malignant melanoma cells, and thereby strongly inhibited their proliferation...
May 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28500235/beta-catenin-inhibitor-bc2059-is-efficacious-as-monotherapy-or-in-combination-with-proteasome-inhibitor-bortezomib-in-multiple-myeloma
#17
Ioanna Savvidou, Tiffany Khong, Andrew Cuddihy, Catriona McLean, Stephen Horrigan, Andrew Spencer
Currently available treatment options are unlikely to be curative for the majority of multiple myeloma (MM) patients, emphasizing a continuing role for the introduction of investigational agents that can overcome drug resistance. The canonical Wnt/beta-catenin signalling pathway, essential for self-renewal, growth and survival, has been found to be dysregulated in MM, particularly in advanced stages of disease. This provides the rationale for evaluating the novel beta-catenin inhibitor BC2059 as monotherapy and in combination with proteasome inhibitors in vitro and in vivo...
May 12, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28491097/wnt5a-signaling-in-normal-and-cancer-stem-cells
#18
REVIEW
Yan Zhou, Thomas J Kipps, Suping Zhang
Wnt5a is involved in activating several noncanonical Wnt signaling pathways, which can inhibit or activate canonical Wnt/β-catenin signaling pathway in a receptor context-dependent manner. Wnt5a signaling is critical for regulating normal developmental processes, including stem cell self-renewal, proliferation, differentiation, migration, adhesion, and polarity. Moreover, the aberrant activation or inhibition of Wnt5a signaling is emerging as an important event in cancer progression, exerting both oncogenic and tumor suppressive effects...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28489928/identification-and-analysis-of-the-%C3%AE-catenin1-gene-in-half-smooth-tongue-sole-cynoglossus-semilaevis
#19
Ying Zhu, Qiaomu Hu, Wenteng Xu, Hailong Li, Hua Guo, Liang Meng, Min Wei, Sheng Lu, Changwei Shao, Na Wang, Guanpin Yang, Songlin Chen
β-catenin is a key signalling molecule in the canonical Wnt pathway, which plays a role in cell adhesion, embryogenesis and sex determination. However, little is known about its function in teleosts. We cloned and characterized the full-length β-catenin1 gene from half-smooth tongue sole (Cynoglossus semilaevis), which was designated CS-β-catenin1. The CS-β-catenin1 cDNA consists of 2,346 nucleotides and encodes a protein with 782 amino acids. Although CS-β-catenin1 was transcribed in the gonads of both sexes, the level was significantly higher in ovaries compared to testes...
2017: PloS One
https://www.readbyqxmd.com/read/28481871/suppression-of-planar-cell-polarity-signaling-and-migration-in-glioblastoma-by-nrdp1-mediated-dvl-polyubiquitination
#20
J H Wald, J Hatakeyama, I Printsev, A Cuevas, W H D Fry, M J Saldana, K VanderVorst, A Rowson-Hodel, J M Angelastro, C Sweeney, K L Carraway Rd
The lethality of the aggressive brain tumor glioblastoma multiforme (GBM) results in part from its strong propensity to invade surrounding normal brain tissue. Although oncogenic drivers such as epidermal growth factor receptor activation and Phosphatase and Tensin homolog inactivation are thought to promote the motility and invasiveness of GBM cells via phosphatidylinostitol 3-kinase activation, other unexplored mechanisms may also contribute to malignancy. Here we demonstrate that several components of the planar cell polarity (PCP) arm of non-canonical Wnt signaling including VANGL1, VANGL2 and FZD7 are transcriptionally upregulated in glioma and correlate with poorer patient outcome...
May 8, 2017: Oncogene
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