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https://www.readbyqxmd.com/read/27904780/low-expression-of-rbms3-and-sfrp1-are-associated-with-poor-prognosis-in-patients-with-gastric-cancer
#1
Tao Zhang, Youliang Wu, Zheng Fang, Qiang Yan, Shangxin Zhang, Ruochuan Sun, Junaid Khaliq, Yongxiang Li
RNA binding motif, single stranded interacting protein 3 (RBMS3) has been reported as a tumor suppressor gene (TSG) in some squamous carcinoma. However, its expression levels and clinical significance in gastric cancer (GC) remains unclear. Secreted frizzled-related protein 1 (SFRP1) plays a role of tumor suppressor in many cancers by inhibiting Wnt/β-catenin pathway. Nevertheless, its expression levels and clinical significance in GC are in dispute. In this study, quantitative real-time PCR and Western Blot were used to measure the mRNA and protein level of RBMS3 and SFRP1 in 23 fresh GC and corresponding normal tissues...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27883247/2-methoxyestradiol-mediated-induction-of-frzb-contributes-to-cell-death-and-autophagy-in-mg63-osteosarcoma-cells
#2
Dalibel Bravo, Kristen L Shogren, Dongqing Zuo, Eric R Wagner, Gobinda Sarkar, Michael J Yaszemski, Avudaiappan Maran
Osteosarcoma is a bone tumor that mainly affects children and adolescents. Although its pathogenesis is still not fully understood, activation of Wnt signaling has been implicated in the development and metastasis of osteosarcoma. In this report, we have investigated the effect of the anti-tumor compound, 2-methoxyestradiol (2-ME) on Wnt antagonist frizzled-related protein b (Frzb), also known as secreted frizzled-related protein (sFRP)3 in human osteosarcoma (MG63) cells. Our results show that 2-ME treatment induces Frzb gene promoter activity, and increases Frzb mRNA and protein levels in osteosarcoma cells...
November 24, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27878554/the-involvement-of-the-decrease-of-astrocytic-wnt5a-in-the-cognitive-decline-in-minimal-hepatic-encephalopathy
#3
Saidan Ding, Zhu Xu, Jianjing Yang, Leping Liu, Xueli Huang, Xuebao Wang, Qichuan Zhuge
Wnt signaling plays a key role in neuroprotection and synaptic plasticity. We speculate that the impairment of Wnt signaling may mediate astrocytic neurotrophins (NTs) production and the impairment of Wnt signaling to astrocytic NTs production contributes to the pathogenesis of minimal hepatic encephalopathy (MHE). Here, we found that induction of astrocytic NTs synthesis was by Wnt5a via the calcium/calmodulin-sensitive protein kinase II (CaMK II)-cAMP-response element-binding protein (CREB) pathway in PCAs...
November 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27869803/genome-wide-crispr-screens-reveal-a-wnt-fzd5-signaling-circuit-as-a-druggable-vulnerability-of-rnf43-mutant-pancreatic-tumors
#4
Zachary Steinhart, Zvezdan Pavlovic, Megha Chandrashekhar, Traver Hart, Xiaowei Wang, Xiaoyu Zhang, Mélanie Robitaille, Kevin R Brown, Sridevi Jaksani, René Overmeer, Sylvia F Boj, Jarrett Adams, James Pan, Hans Clevers, Sachdev Sidhu, Jason Moffat, Stéphane Angers
Forward genetic screens with CRISPR-Cas9 genome editing enable high-resolution detection of genetic vulnerabilities in cancer cells. We conducted genome-wide CRISPR-Cas9 screens in RNF43-mutant pancreatic ductal adenocarcinoma (PDAC) cells, which rely on Wnt signaling for proliferation. Through these screens, we discovered a unique requirement for a Wnt signaling circuit: engaging FZD5, one of the ten Frizzled receptors encoded in the human genome. Our results uncover an underappreciated level of context-dependent specificity at the Wnt receptor level...
November 21, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27859262/functional-and-prognostic-significance-of-the-genomic-amplification-of-frizzled-receptor-6-fzd6-in-breast-cancer
#5
Gabriele Corda, Gianluca Sala, Rossano Lattanzio, Manuela Iezzi, Michele Sallese, Giorgia Fragassi, Alessia Lamolinara, Hasan Mirza, Daniela Barcaroli, Sibylle Ermler, Elisabete Silva, Hemad Yasaei, Robert F Newbold, Paola Vagnarelli, Marcella Mottolese, Pier Giorgio Natali, Letizia Perracchio, Jelmar Quist, Anita Grigoriadis, Pierfrancesco Marra, Andrew N Tutt, Mauro Piantelli, Stefano Iacobelli, Vincenzo De Laurenzi, Arturo Sala
Frizzled receptors mediate Wnt ligands' signalling, which is crucially involved in regulating tissue development, differentiation and is often deregulated in cancer. In this study we found that the Wnt receptor frizzled 6 (FZD6) is frequently amplified in breast cancer, with an increased incidence in the triple negative breast cancer (TNBC) subtype. Ablation of FZD6 gene expression in mammary cancer cell lines: a) inhibited motility and invasion b) induced a more symmetric shape of organoid 3D cultures c) inhibited bone and liver metastasis in vivo...
November 9, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27852064/overexpression-of-fzd7-promotes-glioma-cell-proliferation-by-upregulating-taz
#6
Xia Qiu, Jianguo Jiao, Yidong Li, Tian Tian
Gliomas are the most prevalent type of primary brain tumors in adults, accounting for more than 40% of neoplasm in the central nervous system. Frizzled-7 (FZD7) is a seven-pass trans-membrane Wnt receptor that plays a critical role in the development of various tumors. In this study, we detected high-level FZD7 expression in glioma and its overexpression was associated with advanced tumor stage. In vitro functional assays showed that forced overexpression of FZD7 promoted proliferation of gliomas cells, whereas knockdown of endogenous FZD7 significantly suppressed proliferation ability of these cells...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27849134/developing-and-characterization-of-single-chain-variable-fragment-scfv-antibody-against-frizzled-7-fzd7-receptor
#7
Hamid Nickho, Vahid Younesi, Leili Aghebati-Maleki, Morteza Motallebnezhad, Jafar Majidi Zolbanin, Aliakbar Movassagh Pour, Mehdi Yousefi
Wnt/β-catenin signaling pathway through Frizzled receptors has been shown to play a key role in both normal development and tumorigenesis. Overexpression of Wnt pathway genes, such as Fzd7 in several malignancies is well-documented. Therefore, targeting of Fzd7 and its ligand inhibits cancer cells proliferation metastasis. In the present study we isolated single chain variable fragments (scFvs) against Fzd7 receptor using phage display method. Semi-synthetic human naive antibody libraries (Tomlinson I + J) was employed in panning procedure to isolate specific scFv against specific peptide from extracellular domain of Fzd7 receptor...
November 16, 2016: Bioengineered
https://www.readbyqxmd.com/read/27828711/wnt5a-deficiency-regulates-inflammatory-cytokine-secretion-polarization-and-apoptosis-in-mycobacterium-tuberculosis-infected-macrophages
#8
Deming Chen, Guobao Li, Xiangdong Fu, Pei Li, Jie Zhang, Lan Luo
Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis (MTB), is one of the global public health catastrophes. Wnt signaling has recently been identified to exert immunoregulatory functions in a variety of inflammatory and infectious diseases, including tuberculosis. The opposite expression of Wnt5a in human and mice during MTB infection drives us to explore the roles and biological significances of reduced Wnt5a for MTB-treated mice. In our study, the reduction of WNT5A in MTB-treated mice lung tissues or MTB-infected mice bone marrow-derived macrophages (BM-Mø) was in a dose- and time-dependent manner...
November 9, 2016: DNA and Cell Biology
https://www.readbyqxmd.com/read/27821163/secreted-frizzled-related-protein-2-sfrp2-promotes-osteosarcoma-invasion-and-metastatic-potential
#9
Piti Techavichit, Yang Gao, Lyazat Kurenbekova, Ryan Shuck, Lawrence A Donehower, Jason T Yustein
BACKGROUND: Osteosarcoma (OS), which has a high potential for developing metastatic disease, is the most frequent malignant bone tumor in children and adolescents. Molecular analysis of a metastatic genetically engineered mouse model of osteosarcoma identified enhanced expression of Secreted Frizzled-Related Protein 2 (sFRP2), a putative regulator of Wnt signaling within metastatic tumors. Subsequent analysis correlated increased expression in the human disease, and within highly metastatic OS cells...
November 8, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27814607/molecular-strategies-for-modulating-wnt-signaling
#10
Carl T Gustafson, Tewodros Mamo, Avudaiappan Maran, Michael J Yaszemski
The importance of the Wnt signaling cascade in the fields of developmental biology, regenerative medicine, cancer genetics, and neurobiology has fueled a wide search for potent pharmacological agents capable of controlling Wnt signaling. Numerous fields of study have lent assistance to this endeavor, yielding both natural and synthetic compounds that are capable of inducing or inhibiting Wnt at multiple stages within the pathway. Further, there is a large of body research which has investigated endogenous Wnt inducers and inhibitors, namely the secreted Wnts, Dickkof proteins, secreted Frizzled-Related Proteins, and Wnt Inhibitory Factor-1, along with others which may act via indirect means to stimulate or inhibit Wnt (e...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27793890/heart-peptide-hormones-adjunct-and-primary-treatments-of-cancer
#11
REVIEW
David L Vesely
: Four heart hormones, namely atrial natriuretic peptide (ANP), long-acting natriuretic peptide (LANP), vessel dilator and kaliuretic peptide reduce up to 97% of cancer cells in vitro. These four cardiac hormones eliminate up to 80% of human pancreatic adenocarcinomas, two-thirds of human breast carcinomas and up to 86% of human small-cell lung carcinomas growing in athymic mice. ANP given intravenously for 3 hours after 'curative' lung surgery as an adjunct to surgery results in a 2-year relapse-free survival of 91% compared to 75% for those treated with surgery alone...
November 2016: Anticancer Research
https://www.readbyqxmd.com/read/27786367/isolated-recessive-nail-dysplasia-caused-by-fzd6-mutations-report-of-three-families-and-review-of-the-literature
#12
C Kasparis, D Reid, N J Wilson, V Okur, C Cole, C D Hansen, K Bosse, R C Betz, M Khan, F J D Smith
Congenital abnormalities of the nail are rare conditions that are most frequently associated with congenital ectodermal syndromes involving several of the epidermal appendages including the skin, teeth, hair and nails. Isolated recessive nail dysplasia (IRND) is much rarer but has recently been recognized as a condition resulting in 20-nail dystrophy in the absence of other cutaneous or extracutaneous findings. A few case reports have identified mutations in the Frizzled 6 (FZD6) gene in families presenting with abnormal nails consistent with IRND...
October 27, 2016: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/27758766/fzd7-frizzled-7-expressed-by-endothelial-cells-controls-blood-vessel-formation-through-wnt-%C3%AE-catenin-canonical-signaling
#13
Claire Peghaire, Marie Lise Bats, Raj Sewduth, Sylvie Jeanningros, Beatrice Jaspard, Thierry Couffinhal, Cécile Duplàa, Pascale Dufourcq
OBJECTIVE: Vessel formation requires precise orchestration of a series of morphometric and molecular events controlled by a multitude of angiogenic factors and morphogens. Wnt/frizzled signaling is required for proper vascular formation. In this study, we investigated the role of the Fzd7 (frizzled-7) receptor in retinal vascular development and its relationship with the Wnt/β-catenin canonical pathway and Notch signaling. APPROACH AND RESULTS: Using transgenic mice, we demonstrated that Fzd7 is required for postnatal vascular formation...
October 6, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27746220/collagen-xviii-in-tissue-homeostasis-and-dysregulation-lessons-learned-from-model-organisms-and-human-patients
#14
Ritva Heljasvaara, Mari Aikio, Heli Ruotsalainen, Taina Pihlajaniemi
Collagen XVIII is a ubiquitous basement membrane (BM) proteoglycan produced in three tissue-specific isoforms that differ in their N-terminal non-collagenous sequences, but share collagenous and C-terminal non-collagenous domains. The collagenous domain provides flexibility to the large collagen XVIII molecules on account of multiple interruptions in collagenous sequences. Each isoform has a complex multi-domain structure that endows it with an ability to perform various biological functions. The long isoform contains a frizzled-like (Fz) domain with Wnt-inhibiting activity and a unique domain of unknown function (DUF959), which is also present in the medium isoform...
October 13, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27744318/essential-role-of-the-dishevelled-dep-domain-in-a-wnt-dependent-human-cell-based-complementation-assay
#15
Melissa V Gammons, Trevor J Rutherford, Zachary Steinhart, Stephane Angers, Mariann Bienz
Dishevelled (DVL) assembles Wnt signalosomes through dynamic head-to-tail polymerisation by means of its DIX domain. It thus transduces Wnt signals to cytoplasmic effectors including β-catenin, to control cell fates during normal development, tissue homeostasis and also in cancer. To date, most functional studies of Dishevelled relied on its Wnt-independent signalling activity resulting from overexpression, which is sufficient to trigger polymerisation, bypassing the requirement for Wnt signals. Here, we generate a human cell line devoid of endogenous Dishevelled (DVL1- DVL3), which lacks Wnt signal transduction to β-catenin...
October 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27739564/genetic-variants-in-the-3-untranslated-region-of-sfrp1-gene-and-risk-of-gastric-cancer-in-a-chinese-population
#16
Juan Wu, Junfeng Zhang, Qinhong Cao, Junqin Wang, Zhen Zhan, Zhong Li
BACKGROUND: Secreted frizzled-related protein 1 (sFRP1), a negative regulator of the Wnt signaling pathway, is frequently inactivated in human gastric cancer. Genetic variants in the 3' untranslated region (UTR) of the gene may influence the strength of miRNA binding and the regulation of mRNA transcription, affecting the individual's cancer risk. This study aims to investigate the impact of variants in the 3' UTR of sFRP1 on the gastric cancer susceptibility in a Chinese population. PATIENTS AND METHODS: The association between 2 sFRP1 gene variation loci (rs1127379 and rs10088390) with minor allele frequency more than 0...
October 10, 2016: International Journal of Biological Markers
https://www.readbyqxmd.com/read/27734460/enhancement-of-beta-catenin-in-cardiomyocytes-suppresses-survival-protein-expression-but-promotes-apoptosis-and-fibrosis
#17
James C Lin, Wei-Wen Kuo, Rathinasamy Baskaran, Ming-Cheng Chen, Tsung-Jung Ho, Ray-Jade Chen, Ya-Fang Chen, Viswanadha Vijaya Padma, Ing-Shiow Lay, Chih-Yang Huang
BACKGROUND: Beta-catenin has been implicated in cell-cell communication in a wide variety of developmental and physiological processes. Defective Wnt signaling could result in various cardiac and vascular abnormalities. Little is known regarding Wnt/frizzled pathway in cardiomyocyte apoptosis. METHODS: In this study, the role of β-catenin in apoptosis was investigated in H9c2 cardiomyocytes and primary cardiomyocytes isolated in diabetic Wistar rats. The cardiomyocytes were transfected with porcine cytomegalovirus (pCMV)-β-catenin plasmid in order to overexpress β-catenin...
October 13, 2016: Cardiology Journal
https://www.readbyqxmd.com/read/27733096/endogenous-dkk1-and-frzb-regulate-chondrogenesis-and-hypertrophy-in-three-dimensional-cultures-of-human-chondrocytes-and-human-mesenchymal-stem-cells
#18
Leilei Zhong, Xiaobin Huang, Emilie Dooms Rodrigues, Jeroen C H Leijten, Theo Verrips, Mohamed El Khattabi, Marcel Karperien, Janine N Post
Hypertrophic differentiation occurs during in vitro chondrogenesis of mesenchymal stem cells (MSCs), decreasing the quality of the cartilage construct. Previously we identified WNT pathway antagonists Dickkopf 1 homolog (DKK1) and frizzled-related protein (FRZB) as key factors in blocking hypertrophic differentiation of human MSCs (hMSCs). In this study, we investigated the role of endogenously expressed DKK1 and FRZB in chondrogenesis of hMSC and chondrocyte redifferentiation and in preventing cell hypertrophy using three relevant human cell based systems, isolated hMSCs, isolated primary human chondrocytes (hChs), and cocultures of hMSCs with hChs for which we specifically designed neutralizing nano-antibodies...
December 1, 2016: Stem Cells and Development
https://www.readbyqxmd.com/read/27720921/hesperidin-derivative-11-inhibits-fibroblast-like-synoviocytes-proliferation-by-activating-secreted-frizzled-related-protein-2-in-adjuvant-arthritis-rats
#19
Yanhui Liu, Zhenghao Sun, Dandan Xu, Junda Liu, Xiaofeng Li, Xiaoqin Wu, Yilong Zhang, Qianqian Wang, Cheng Huang, Xiaoming Meng, Jun Li
Hesperidin (HDN), a flavanone glycoside derived from the citrus cultivation, has a multitude of pharmacological properties, which include antioxidant, anti-inflammatory, hypolipidaemic and anti-carcinogenic actions, but the underlying mechanisms by which treatment of HDN attenuates Rheumatoid Arthritis (RA) remain elusive. Here we engaged to determine whether Hesperidin derivative-11(HDND-11), a HDN derivative with enhanced water-solubility and bioavailability, is effective on treating arthritis in rats. In this study, results of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetra-zolium bromide (MTT) assay and Flow cytometry indicated that administration of HDND-11 inhibited proliferation of fibroblast-like synoviocytes (FLS)...
October 7, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27720905/a-dynamic-wnt-%C3%AE-catenin-signaling-environment-leads-to-wnt-independent-and-wnt-dependent-proliferation-of-embryonic-intestinal-progenitor-cells
#20
Alana M Chin, Yu-Hwai Tsai, Stacy R Finkbeiner, Melinda S Nagy, Emily M Walker, Nicole J Ethen, Bart O Williams, Michele A Battle, Jason R Spence
Much of our understanding about how intestinal stem and progenitor cells are regulated comes from studying the late fetal stages of development and the adult intestine. In this light, little is known about intestine development prior to the formation of stereotypical villus structures with columnar epithelium, a stage when the epithelium is pseudostratified and appears to be a relatively uniform population of progenitor cells with high proliferative capacity. Here, we investigated a role for WNT/β-CATENIN signaling during the pseudostratified stages of development (E13...
November 8, 2016: Stem Cell Reports
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