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https://www.readbyqxmd.com/read/28230864/dicer-promotes-tumorigenesis-by-translocating-to-nucleus-to-promote-sfrp1-promoter-methylation-in-cholangiocarcinoma-cells
#1
Wenlong Cheng, Yongqiang Qi, Li Tian, Bing Wang, Wenhua Huang, Yongjun Chen
Dicer, a member of the RNase III family of endoribonucleases, has an important role in regulating methylation of CpG islands in mammal cancer cells. However, the underlying mechanism of action remains unclear. In this study, we demonstrated that upregulation of Dicer in cholangiocarcinoma (CCA) cells and its translocation to nuclues to interact with heterochromatin protein 1α (HP1α). The nuclear Dicer/HP1α complex appeared to promote both H3K9 trimethylation and DNA methylation of the secreted frizzled-related protein 1 (SFRP1) promoter...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28229087/modeling-williams-syndrome-with-induced-pluripotent-stem-cells
#2
Thanathom Chailangkarn, Alysson R Muotri
The development of induced pluripotent stem cells (iPSCs) like never before has opened novel opportunity to study diseases in relevant cell types. In our recent study, Williams syndrome (WS), a rare genetic neurodevelopmental disorder, that is caused by hemizygous deletion of 25-28 genes on chromosome 7, is of interest because of its unique cognitive and social profiles. Little is known about haploinsufficiency effect of those deleted genes on molecular and cellular phenotypes at the neural level due to the lack of relevant human cellular model...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28218291/a-pan-cancer-analysis-of-secreted-frizzled-related-proteins-re-examining-their-proposed-tumour-suppressive-function
#3
Krista Marie Vincent, Lynne-Marie Postovit
Secreted frizzled-related proteins (SFRPs), containing five family members (SFRPs 1-5) are putative extracellular Wnt inhibitors. Given their abilities to inhibit Wnt signalling, as well as the loss of SFRP1 in many cancers, this family is generally considered to be tumour suppressive. In this study we analyzed gene expression, promoter methylation and survival data from over 8000 tumour and normal samples from 29 cancers in order to map the context-specific associations of SFRPs 1-5 with patient survival, gene silencing and gene expression signatures...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28217097/feedback-activation-of-basic-fibroblast-growth-factor-signaling-via-the-wnt-%C3%AE-catenin-pathway-in-skin-fibroblasts
#4
Xu Wang, Yuting Zhu, Congcong Sun, Tao Wang, Yingjie Shen, Wanhui Cai, Jia Sun, Lisha Chi, Haijun Wang, Na Song, Chao Niu, Jiayi Shen, Weitao Cong, Zhongxin Zhu, Yuanhu Xuan, Xiaokun Li, Litai Jin
Skin wound healing is a complex process requiring the coordinated behavior of many cell types, especially in the proliferation and migration of fibroblasts. Basic fibroblast growth factor (bFGF) is a member of the FGF family that promotes fibroblast migration, but the underlying molecular mechanism remains elusive. The present RNA sequencing study showed that the expression levels of several canonical Wnt pathway genes, including Wnt2b, Wnt3, Wnt11, T-cell factor 7 (TCF7), and Frizzled 8 (FZD8) were modified by bFGF stimulation in fibroblasts...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28209772/maternal-smoke-exposure-decreases-mesenchymal-proliferation-and-modulates-rho-gtpase-dependent-actin-cytoskeletal-signaling-in-fetal-lungs
#5
Uchenna Unachukwu, Jordis Trischler, Monica Goldklang, Rui Xiao, Jeanine D'Armiento
The present study tested the hypothesis that maternal smoke exposure results in fetal lung growth retardation due to dysregulation in various signaling pathways, including the Wnt (wingless-related integration site)/β-catenin pathway. Pregnant female C57BL/6J mice were exposed to cigarette smoke (100-150 mg/m(3)) or room air, and offspring were humanely killed on 12.5, 14.5, 16.5, and 18.5 d post coitum (dpc). We assessed lung stereology with Cavalieri estimation; apoptosis with proliferating cell nuclear antigen, TUNEL, and caspase assays; and gene expression with quantitative PCR (qPCR) and RNA sequencing on lung epithelium and mesenchyme retrieved by laser capture microdissection...
February 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28208209/the-emergence-of-tnik-inhibitors-in-cancer-therapeutics
#6
REVIEW
Tesshi Yamada, Mari Masuda
The outcome of patients with metastatic colorectal cancer remains unsatisfactory. To improve patient prognosis, it will be necessary to identify new drug targets based on molecules that are essential for colorectal carcinogenesis, and to develop therapeutics that target such molecules. The great majority of colorectal cancers (>90%) have mutations in at least one Wnt signaling pathway gene. Aberrant activation of Wnt signaling is a major force driving colorectal carcinogenesis. Several therapeutics targeting Wnt pathway molecules, including porcupine, frizzled receptors, and tankyrases, have been developed, but none of them have yet been incorporated into clinical practice...
February 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28197104/angled-growth-of-the-dental-lamina-is-accompanied-by-asymmetrical-expression-of-the-wnt-pathway-receptor-frizzled-6
#7
Iveta Putnová, Hana Dosedělová, Vitezslav Bryja, Marie Landová, Marcela Buchtová, Jan Štembírek
Frizzled 6 (FZD6) belongs to a family of proteins that serve as receptors in the WNT signaling pathway. FZD6 plays an important role in the establishment of planar cell polarity in many embryonic processes such as convergent extension during gastrulation, neural tube closure, or hair patterning. Based on its role during hair development, we hypothesized that FZD6 may have similar expression pattern and function in the dental lamina, which is also a distinct epithelial protrusion growing characteristically angled into the mesenchyme...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28178355/effects-of-exercise-training-on-circulating-levels-of-dickkpof-1-and-secreted-frizzled-related-protein-1-in-breast-cancer-survivors-a-pilot-single-blind-randomized-controlled-trial
#8
Tae Ho Kim, Jae Seung Chang, Kyu-Sang Park, Jeeyeon Park, Nahyun Kim, Jong In Lee, In Deok Kong
BACKGROUND: Wingless and integration site growth factor (Wnt) signaling is a tumorigenesis-related signaling pathway. Dickkpof-1 (DKK1) and secreted frizzled-related protein-1 (SFRP1) are endogenous negative regulators of Wnt/β-catenin signaling. Accumulating evidence indicates that higher serum levels of DKK1 are correlated with poor prognosis of various types of cancer. Here, we investigated whether exercise training causes changes in the serum levels of DKK1 and SFRP1 in patients with breast cancer...
2017: PloS One
https://www.readbyqxmd.com/read/28177772/-i-frizzled-i-gene-expression-and-negative-regulation-of-canonical-wnt-%C3%AE-%C3%AF-catenin-signaling-in-mouse-f9-teratocarcinoma-cells
#9
Gregory Golenia, Mohamed I Gatie, Gregory M Kelly
Mouse F9 cells differentiate into primitive endoderm (PrE) following the activation of the canonical WNT/β-catenin pathway. The upregulation of <i>Wnt6</i> and activation of β-catenin-TCF/LEF-dependent transcription is known to accompany differentiation, but the Frizzled (FZD) receptor responsible for transducing the WNT6 signal is not known. Eight of the ten <i>Fzd</i> genes were found to be expressed in F9 cells, with <i>Fzd7</i> being the most highly expressed, and chosen for further analysis...
September 13, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28169332/secreted-frizzled-related-protein-1-overexpression-in-gastric-cancer-relationship-with-radiological-findings-of-dual-energy-spectral-ct-and-pet-ct
#10
Huimin Lin, Guoyuan Yang, Bei Ding, Miao Zhang, Mingjun Zhang, Fuhua Yan, Ying Qu, Huan Zhang
We explored the role of secreted frizzled-related protein 1 (sFRP1) overexpression in gastric cancer and its relationship with radiological findings from dual-energy spectral CT(DEsCT) and positron emission tomography/computed tomography (PET/CT). We established mouse metastatic models using the SGC-7901/sFRP1 gastric cancer cell line. A control group was established using the SGC-7901/vector cell line. The models were then scanned with dual-energy spectral CT and PET-CT. Subsequent analysis, including immunohistochemistry and Transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL), was performed to confirm the role of sFRP1...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28153580/from-planar-cell-polarity-to-ciliogenesis-and-back-the-curious-tale-of-the-ppe-and-cplane-proteins
#11
REVIEW
Paul N Adler, John B Wallingford
Why some genes are more popular than others remains an open question, but one example of this phenomenon involves the genes controlling planar cell polarity (PCP), the polarization of cells within a plane of a tissue. Indeed, the so-called 'core' PCP genes such as dishevelled, frizzled, and prickle have been extensively studied both in animal models and by human genetics. By contrast, other genes that influence PCP signaling have received far less attention. Among the latter are inturned, fuzzy, and fritz, but recent work should bring these once obscure regulators into the limelight...
January 30, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28153008/correlation-of-blood-bone-turnover-biomarkers-and-wnt-signaling-antagonists-with-as-dish-opll-and-oyl
#12
Chi-Chien Niu, Song-Shu Lin, Li-Jen Yuan, Lih-Huei Chen, Chuen-Yung Yang, An-Ni Chung, Meng-Ling Lu, Tsung-Ting Tsai, Po-Liang Lai, Wen-Jer Chen
BACKGROUND: Wnt signaling plays an important role in development and maintenance of many organs and tissues. The most-studied secreted Wnt inhibitors are sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), and secreted frizzled related protein 1 (SFRP-1) which play important roles in bone turnover. The present study investigated the relationship between serum Wnt inhibitors and diseases with excessive ossification structures, such as ossification of posterior longitudinal ligament (OPLL), ankylosing spondylitis (AS), diffuse idiopathic skeletal hyperostosis (DISH), and ossification of yellow ligament (OYL)...
February 2, 2017: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/28151034/sfrp3-and-dkk1-regulate-fibroblast-like-synoviocytes-markers-and-wnt-elements-expression-depending-on-cellular-context
#13
Dorra Elhaj Mahmoud, Nadia Sassi, Ghassen Drissi, Maher Barsaoui, Khaled Zitouna, Hela Sahli, Maryam Kallel-Sellami, Lassad Kanoun, Elhem Cheour, Lilia Laadhar
CONTEXT: Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) display pathogenic behavior. Various members of the Wnt pathway, especially the canonical Wnt/β-catenin cascade, may contribute to autonomous RA FLS activation. It has been shown that the two Wnt inhibitors: sFRP3 and DKK1 contribute to several critical aspects of joint biology. However, their effects on RA FLS are poorly characterized. The aim of our study was to investigate the effects of sFRP3 and DKK1 on FLS markers, Wnt components, and target oncogenes expression by RA FLS and compare the findings to osteoarthritic (OA) FLS...
February 2, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28147310/colorectal-cancer-cells-suppress-cd4-t-cells-immunity-through-canonical-wnt-signaling
#14
Xuan Sun, Suoning Liu, Daguang Wang, Yang Zhang, Wei Li, Yuchen Guo, Hua Zhang, Jian Suo
Understanding how colorectal cancer escapes from immunosurveillance and immune attack is important for developing novel immunotherapies for colorectal cancer. In this study we evaluated the role of canonical Wnt signaling in the regulation of T cell function in a mouse colorectal cancer model. We found that colorectal cancer cells expressed abundant Wnt ligands, and intratumoral T cells expressed various Frizzled proteins. Meanwhile, both active β-catenin and total β-catenin were elevated in intratumoral T cells...
January 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28126591/fzd10-g%C3%AE-13-signalling-axis-points-to-a-role-of-fzd10-in-cns-angiogenesis
#15
Belma Hot, Jana Valnohova, Elisa Arthofer, Katharina Simon, Jaekyung Shin, Mathias Uhlén, Evi Kostenis, Jan Mulder, Gunnar Schulte
Among the 10 Frizzled (FZD) isoforms belonging to the Class F of G protein-coupled receptors (GPCRs), FZD10 remains the most enigmatic. FZD10 shows homology to FZD4 and FZD9 and was previously implicated in both β-catenin-dependent and -independent signalling. In normal tissue, FZD10 levels are generally very low; however, its upregulation in synovial carcinoma has attracted some attention for therapy. Our findings identify FZD10 as a receptor interacting with and signalling through the heterotrimeric G protein Gα13 but not Gα12, Gαi1, GαoA, Gαs, or Gαq...
January 24, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28120389/modulating-the-wnt-signaling-pathway-with-small-molecules
#16
REVIEW
Freddi Huan Tran, Jie J Zheng
Wnt signaling is a critical component during embryonic development and also plays an important role in regulating adult tissue homeostasis. Abnormal activation of Wnt signaling has been implicated in many cancers, while reduced activity of Wnt signaling leads to poor wound healing and structural formations. Thus, extensive efforts have been focused on developing small molecules that have potential to either inhibit or activate the pathway, hoping these molecules can offer leads for novel approaches in treating different human diseases...
January 25, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28109136/therapeutic-potential-of-targeting-wnt-%C3%AE-catenin-pathway-in-treatment-of-colorectal-cancer-rational-and-progress
#17
Afsane Bahrami, Forouzan Amerizadeh, Soodabeh ShahidSales, Majid Khazaei, Majid Ghayour-Mobarhan, Hamid Reza Sadeghnia, Mina Maftouh, Seyed Mahdi Hassanian, Amir Avan
Wnt/β-catenin pathway is one of the main/frequent dysregulated pathways in several tumor types, including colon cancer. Aberrant activation of this pathway is associated with cell proliferation, invasive behaviors and cell resistance, suggesting its potential value as a therapeutic target in treatment of CRC. Several agents have been developed for targeting of this pathway (e.g, natural agents: curcumin, 3,3-diindolylmethane, phytoestrogen; Synthetic/small Wnt inhibitors: Rofecoxib; PRI-724, CWP232291; and monoclonal antibody against frizzled receptors, Vanituctumab...
January 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28100910/a-novel-sequence-variant-in-sfrp4-causing-pyle-disease
#18
Chelna Galada, Hitesh Shah, Anju Shukla, Katta M Girisha
Pyle disease (PYL) is an extremely rare disorder of irregular development of long bone. Recently, homozygous mutations in secreted frizzled-related protein 4 gene (SFRP4) gene were found to underlie this condition. Sequencing of coding regions of SFRP4 gene from an 11-year-old female with PYL was performed. A novel homozygous nonsense variant, c.183C>G (p.Y61*) was observed. Segregation analysis in the patient revealed a germline mutation, resulting in reduced protein formation. This is the second report from a fourth affected family with a SFRP4 mutation causing PYL disease...
January 19, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/28095260/differential-expression-and-roles-of-secreted-frizzled-related-protein-5-and-the-wingless-homolog-wnt5a-in-periodontitis
#19
T Maekawa, P Kulwattanaporn, K Hosur, H Domon, M Oda, Y Terao, T Maeda, G Hajishengallis
The Wingless/integrase-1 (Wnt) family of protein ligands and their functional antagonists, secreted frizzled-related proteins (sFRPs), regulate various biological processes ranging from embryonic development to immunity and inflammation. Wnt5a and sFRP5 comprise a typical ligand/antagonist pair, and the former molecule was recently detected at the messenger RNA (mRNA) level in human periodontitis. The main objective of this study was to investigate the interrelationship of expression of Wnt5a and sFRP5 in human periodontitis (as compared to health) and to determine their roles in inflammation and bone loss in an animal model...
January 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28079285/a-pathway-based-association-study-reveals-variants-from-wnt-signaling-genes-contributing-to-asthma-susceptibility
#20
A Barreto-Luis, A Corrales, M Acosta-Herrera, C Gonzalez-Colino, J Cumplido, J Martinez-Tadeo, A Carracedo, J Villar, T Carrillo, M Pino-Yanes, C Flores
BACKGROUND: Genetic susceptibility to asthma is currently linked to a handful of genes which have a limited ability to predict the overall disease risk, suggesting the existence of many other genes involved in disease development. Accumulated evidence from association studies in genes related by biological pathways could reveal novel asthma genes. OBJECTIVE: To reveal novel asthma susceptibility genes by means of a pathway-based association study. METHODS: Based on summary data from a previous a genome-wide association study (GWAS) of asthma, we first identified significant biological pathways using a gene-set enrichment analysis...
January 12, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
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