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https://www.readbyqxmd.com/read/28534940/the-wnt-regulator-sfrp4-inhibits-mesothelioma-cell-proliferation-migration-and-antagonizes-wnt3a-via-its-netrin-like-domain
#1
Vanathi Perumal, Arun M Dharmarajan, Simon A Fox
Secreted frizzled related proteins (SFRPs) are a family of Wnt regulators which are frequently downregulated in cancers. In malignant mesothelioma (MM), downregulation of SFRP4 has been reported as a mechanism which contributes to aberrant activation of oncogenic Wnt signaling. Here we investigated the biological consequences of SFRP4 in two mesothelioma cell models where this protein is downregulated. We used recombinant SFRP4 and transient overexpression to study changes in proliferation, migration and downstream signaling...
May 18, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28533339/structure-based-prediction-of-wnt-binding-affinities-for-frizzled-type-cysteine-rich-domain
#2
Mark Agostino, Sebastian Öther-Gee Pohl, Arunasalam Dharmarajan
Wnt signaling pathways are of significant interest in development and oncogenesis. The first step in these pathways typically involves the binding of a Wnt protein to the cysteine-rich domain (CRD) of a Frizzled receptor; Wnt-Frizzled interactions can be antagonized by secreted Frizzled-related proteins (sFRPs), which also contain a Frizzled-like CRD. The large number of Wnts, Frizzleds and sFRPs, as well as the hydrophobic nature of Wnt, pose challenges to laboratory-based investigations of interactions involving Wnt...
May 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28532817/-pro-renin-receptor-as-a-therapeutic-target-for-the-treatment-of-cardiovascular-diseases
#3
REVIEW
Yuan Sun, A H Jan Danser, Xifeng Lu
The discovery of the (pro)renin receptor [(P)RR] 15years ago stimulated ideas on prorenin being more than renin's inactive precursor. Indeed, binding of prorenin to the (P)RR induces a conformational change in the prorenin molecule, allowing it to display angiotensin-generating activity, and additionally results in intracellular signaling in an angiotensin-independent manner. However, the prorenin levels required to observe these angiotensin-dependent and -independent effects of the (P)RR are many orders above its in vivo concentrations, both under normal and pathological conditions...
May 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28468589/forced-expression-of-wnt-antagonists-sfrp1-and-wif1-sensitizes-chronic-myeloid-leukemia-cells-to-tyrosine-kinase-inhibitors
#4
Melek Pehlivan, Ceyda Caliskan, Zeynep Yuce, Hakkı Ogun Sercan
Chronic myeloid leukemia is a clonal myeloproliferative disorder that arises from the neoplastic transformation of the hematopoietic stem cell, in which the Wnt/β-catenin signaling pathway has been demonstrated to play an important role in disease progression. However, the role of Wnt signaling antagonists in therapy resistance and disease progression has not been fully investigated. We aimed to study the effects of Wnt/β-catenin pathway antagonists-secreted frizzled-related protein 1 and Wnt inhibitory factor 1-on resistance toward tyrosine kinase inhibitors in chronic myeloid leukemia...
May 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28467820/non-equivalence-of-wnt-and-r-spondin-ligands-during-lgr5-intestinal-stem-cell-self-renewal
#5
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/28467818/surrogate-wnt-agonists-that-phenocopy-canonical-wnt-and-%C3%AE-catenin-signalling
#6
Claudia Y Janda, Luke T Dang, Changjiang You, Junlei Chang, Wim de Lau, Zhendong A Zhong, Kelley S Yan, Owen Marecic, Dirk Siepe, Xingnan Li, James D Moody, Bart O Williams, Hans Clevers, Jacob Piehler, David Baker, Calvin J Kuo, K Christopher Garcia
Wnt proteins modulate cell proliferation and differentiation and the self-renewal of stem cells by inducing β-catenin-dependent signalling through the Wnt receptor frizzled (FZD) and the co-receptors LRP5 and LRP6 to regulate cell fate decisions and the growth and repair of several tissues. The 19 mammalian Wnt proteins are cross-reactive with the 10 FZD receptors, and this has complicated the attribution of distinct biological functions to specific FZD and Wnt subtype interactions. Furthermore, Wnt proteins are modified post-translationally by palmitoylation, which is essential for their secretion, function and interaction with FZD receptors...
May 11, 2017: Nature
https://www.readbyqxmd.com/read/28463110/the-sec14-like-phosphatidylinositol-transfer-proteins-sec14l3-sec14l2-act-as-gtpase-proteins-to-mediate-wnt-ca-2-signaling
#7
Bo Gong, Weimin Shen, Wanghua Xiao, Yaping Meng, Anming Meng, Shunji Jia
The non-canonical Wnt/Ca(2+) signaling pathway plays important roles in embryonic development, tissue formation and diseases. However, it is unclear how the Wnt ligand-stimulated, G protein-coupled receptor Frizzled activates phospholipases for calcium release. Here, we report that the zebrafish/human phosphatidylinositol transfer protein Sec14l3/SEC14L2 act as GTPase proteins to transduce Wnt signals from Frizzled to phospholipase C (PLC). Depletion of sec14l3 attenuates Wnt/Ca(2+) responsive activity and causes convergent and extension (CE) defects in zebrafish embryos...
May 2, 2017: ELife
https://www.readbyqxmd.com/read/28427856/frizzled-3-acts-upstream-of-alcam-during-embryonic-eye-development
#8
Franziska A Seigfried, Wiebke Cizelsky, Astrid S Pfister, Petra Dietmann, Paul Walther, Michael Kühl, Susanne J Kühl
Formation of a functional eye during vertebrate embryogenesis requires different processes such as cell differentiation, cell migration, cell-cell interactions as well as intracellular signalling processes. It was previously shown that the non-canonical Wnt receptor Frizzled 3 (Fzd3) is required for proper eye formation, however, the underlying mechanism is poorly understood. Here we demonstrate that loss of Fzd3 induces severe malformations of the developing eye and that this defect is phenocopied by loss of the activated leukocyte cell adhesion molecule (Alcam)...
April 17, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28425477/microrna-27a-3p-modulates-the-wnt-%C3%AE-catenin-signaling-pathway-to-promote-epithelial-mesenchymal-transition-in-oral-squamous-carcinoma-stem-cells-by-targeting-sfrp1
#9
Bin Qiao, Bao-Xia He, Jing-Hua Cai, Qian Tao, Alfred King-Yin Lam
This study aimed to elucidate how microRNA27a-3p (miR-27a-3p) modulates the Wnt/β-catenin signaling pathway to promote the epithelial-mesenchymal transition (EMT) in oral squamous carcinoma stem cells (OSCSCs) by targeting secreted frizzled-related protein 1 (SFRP1). Flow cytometry was used to sort OSCSCs from the SCC-9 and Tca8113 cell lines. The OSCSCs were randomly assigned into the miR-27a-3p inhibitors group, the miR-27a-3p inhibitors-NC group, the si-SFRP1 group, the si-SFRP1 + miR-27a-3p inhibitors group and the blank group...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28418908/plasma-protein-profiling-in-patients-undergoing-coronary-artery-bypass-grafting-surgery-and-clinical-significance
#10
Zhi-Peng Guo, Hai-Tao Hou, Rui Jing, Zhen-Guo Song, Xiao-Cheng Liu, Guo-Wei He
This study was designed to identify the protein profiling in patients with triple vessel coronary artery disease (CAD) undergoing CABG, in order to detect CAD-related differential proteins in these patients. CABG patients with triple vessel disease with/without left main stenosis (n =160) were compared to normal coronary angiographic subjects (n =160). Plasma samples of 20 males and 20 females in each group were analyzed with iTRAQ technique. ELISA test was used to test the chosen proteins from iTRAQ results in plasma samples from a new cohort of the CABG group (n=120, male/femal=61/59) and control (n =120, male/female=60/60)...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28403963/the-wnt-%C3%AE-catenin-signaling-pathway-may-be-involved-in-granulosa-cell-apoptosis-from-patients-with-pcos-in-north-china
#11
X-Q Wu, Y-Q Wang, S-M Xu, J-F Liu, X-Y Bi, Z-Q Wang, J-P Zhang
INTRODUCTION: Investigate the expressions of WNTs in granulosa cells of PCOS in North China, and explore the possible mechanism. MATERIAL AND METHODS: Patients with PCOS (n=40) and controls without PCOS (n=20) were enrolled into the study. The levels of serum sex hormone were detected by chemiluminescent enzyme immunoassay. RT-qPCR was used to measure mRNA levels of WNT family members (WNT1, WNT3, WNT4, WNT5, sFRP4 and sFRP5). The levels of Bax and Bcl-2 were measured by enzyme-linked immunosorbent assay...
January 2017: J Gynecol Obstet Hum Reprod
https://www.readbyqxmd.com/read/28398872/hydrogen-peroxide-induced-secreted-frizzled-related-protein-1-gene-demethylation-contributes-to-hydrogen-peroxide-induced-apoptosis-in-human-u251-glioma-cells
#12
Zhiguo Xing, Yaping Ni, Junjie Zhao, Xudong Ma
Glioblastoma multiforme is a type of central nervous system tumor with extremely poor prognosis. Previously, hydrogen peroxide (H2O2), which promotes the oxidative stress response, has been reported to induce the apoptosis of glioma cells. Recently, secreted frizzled-related protein 1 (SFRP1) has been shown to be associated with various types of malignant tumors and with H2O2-induced oxidative stress in cardiomyocytes by negatively regulating the Wnt signaling pathway. This study aimed to explore SFRP1 expression and its roles in H2O2-induced apoptosis in human glioma cells...
May 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28386775/intermittent-pacing-therapy-favorably-modulates-infarct-remodeling
#13
André Uitterdijk, Tirza Springeling, Kevin C M Hermans, Daphne Merkus, Vincent J de Beer, Charlotte Gorsse-Bakker, Eric Mokelke, Evangelos P Daskalopoulos, Piotr A Wielopolski, Jack P M Cleutjens, W Matthijs Blankesteijn, Frits W Prinzen, Willem J van der Giessen, Robert-Jan M van Geuns, Dirk J Duncker
Despite early revascularization, remodeling and dysfunction of the left ventricle (LV) after acute myocardial infarction (AMI) remain important therapeutic targets. Intermittent pacing therapy (IPT) of the LV can limit infarct size, when applied during early reperfusion. However, the effects of IPT on post-AMI LV remodeling and infarct healing are unknown. We therefore investigated the effects of IPT on global LV remodeling and infarct geometry in swine with a 3-day old AMI. For this purpose, fifteen pigs underwent 2 h ligation of the left circumflex coronary artery followed by reperfusion...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28385590/characterization-and-expression-pattern-of-a-novel-frizzled-8-receptor-gene-in-schistosoma-japonicum
#14
Jingxiu Xu, Xingang Feng, Yingying Jia, Yang Hong, Hao Li, Ke Lu, Jiaojiao Lin, Chunxiu Yuan, Mingxin Song
Wnt signaling as mediated by the Frizzled family receptors plays a vital role in the early development of animal embryos, organ formation, tissue regeneration and other physiological processes. In the present study, a novel Frizzled member, SjFz8, was isolated and characterized in Schistosoma japonicum. SjFz8 encodes an 1162-amino-acid protein with typical characteristics of Frizzled proteins. Quantitative real-time polymerase chain reaction analysis indicated that SjFz8 transcript level was highest in 7-day-old schistosomula...
April 3, 2017: Parasitology International
https://www.readbyqxmd.com/read/28384160/a-wnt-planar-polarity-pathway-instructs-neurite-branching-by-restricting-f-actin-assembly-through-endosomal-signaling
#15
Chun-Hao Chen, Chun-Wei He, Chien-Po Liao, Chun-Liang Pan
Spatial arrangement of neurite branching is instructed by both attractive and repulsive cues. Here we show that in C. elegans, the Wnt family of secreted glycoproteins specify neurite branching sites in the PLM mechanosensory neurons. Wnts function through MIG-1/Frizzled and the planar cell polarity protein (PCP) VANG-1/Strabismus/Vangl2 to restrict the formation of F-actin patches, which mark branching sites in nascent neurites. We find that VANG-1 promotes Wnt signaling by facilitating Frizzled endocytosis and genetically acts in a common pathway with arr-1/β-arrestin, whose mutation results in defective PLM branching and F-actin patterns similar to those in the Wnt, mig-1 or vang-1 mutants...
April 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28377511/unsaturated-fatty-acyl-recognition-by-frizzled-receptors-mediates-dimerization-upon-wnt-ligand-binding
#16
Aaron H Nile, Susmith Mukund, Karen Stanger, Weiru Wang, Rami N Hannoush
Frizzled (FZD) receptors mediate Wnt signaling in diverse processes ranging from bone growth to stem cell activity. Moreover, high FZD receptor expression at the cell surface contributes to overactive Wnt signaling in subsets of pancreatic, ovarian, gastric, and colorectal tumors. Despite the progress in biochemical understanding of Wnt-FZD receptor interactions, the molecular basis for recognition of Wnt cis-unsaturated fatty acyl groups by the cysteine-rich domain (CRD) of FZD receptors remains elusive. Here, we determined a crystal structure of human FZD7 CRD unexpectedly bound to a 24-carbon fatty acid...
April 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28373995/dickkopf-1-is-a-biomarker-for-systemic-lupus-erythematosus-and-active-lupus-nephritis
#17
Jing Xue, Jiali Yang, Lijuan Yang, Shaolan Zhou, Chen Ji, Xuemei Wang, Nan Yu, Xiaoming Liu, Shuhong Chi
An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the concentrations of Wnt-3A, Frizzled-8 (FZD-8), and Dickkopf-1 (DKK-1) of Wnt signaling, as well as their diagnostic values for accessing LN, were evaluated by ELISA in sera and urine of 111 SLE patients (31 with LN and 80 without LN) and 70 healthy cohorts. Significantly more abundances of DKK-1 protein were determined in both of sera and urine of SLE patients compared to healthy cohorts (p < 0...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28373842/breast-cancer-stem-like-cells-are-inhibited-by-diosgenin-a-steroidal-saponin-by-the-attenuation-of-the-wnt-%C3%AE-catenin-signaling-via-the-wnt-antagonist-secreted-frizzled-related-protein-4
#18
G Bhuvanalakshmi, Basappa, Kanchugarakoppal S Rangappa, Arun Dharmarajan, Gautam Sethi, Alan P Kumar, Sudha Warrier
Background: Identification of breast cancer stem cells as the chemo-resistant and tumor-initiating population represents an important milestone in approaching anticancer therapies. Targeting this minor subpopulation of chemo- and radio-resistant stem-like cells, termed as the cancer stem cells (CSCs) and their eradication could significantly enhance clinical outcomes. Most of the presently administered chemotherapeutics target the tumor bulk but are ineffective against the CSCs. We report here that diosgenin (DG), a naturally occurring steroidal saponin, could effectively inhibit CSCs from three breast cancer cell lines, MCF7, T47D and MDA-MB-231, by inducing apoptosis and inhibiting the CSC associated phenotypes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28368424/p53-rb-inhibition-induces-metastatic-adrenocortical-carcinomas-in-a-preclinical-transgenic-model
#19
M Batisse-Lignier, I Sahut-Barnola, F Tissier, T Dumontet, M Mathieu, C Drelon, J-C Pointud, C Damon-Soubeyrand, G Marceau, J-L Kemeny, J Bertherat, I Tauveron, P Val, A Martinez, A-M Lefrançois-Martinez
Adrenocortical carcinoma (ACC) is a rare cancer with poor prognosis. Pan-genomic analyses identified p53/Rb and WNT/β-catenin signaling pathways as main contributors to the disease. However, isolated β-catenin constitutive activation failed to induce malignant progression in mouse adrenocortical tumors. Therefore, there still was a need for a relevant animal model to study ACC pathogenesis and to test new therapeutic approaches. Here, we have developed a transgenic mice model with adrenocortical specific expression of SV40 large T-antigen (AdTAg mice), to test the oncogenic potential of p53/Rb inhibition in the adrenal gland...
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28359679/activation-of-wnt-signaling-increases-numbers-of-enteric-neurons-derived-from-neonatal-mouse-and-human-progenitors%C3%A2-cells
#20
Ying Zhang, Karin Seid, Florian Obermayr, Lothar Just, Peter H Neckel
BACKGROUND & AIMS: Neural stem and progenitor cells from the enteric nervous system (ENS) might serve as a source of cells for treatment of neurogastrointestinal disorders. Before we can use these cells, we must increase our understanding of the signaling mechanisms that regulate proliferation and differentiation. We systematically evaluated the effects of canonical Wnt signaling on proliferation and differentiation of cultured ENS progenitor cells from neonatal mice and humans. METHODS: We isolated ENS progenitors from tunica muscularis of the small intestine of newborn (postnatal day 0) wild-type C57BL/6 mice as well as from Wnt1-Cre2 reporter mice...
March 27, 2017: Gastroenterology
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