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https://www.readbyqxmd.com/read/28635355/aberrant-wnt-signaling-a-special-focus-in-cns-diseases
#1
Mercedes Arnés, Sergio Casas Tintó
Wnt signals regulate cell proliferation, migration and differentiation during development, as well as synaptic transmission and plasticity in the adult brain. Abnormal Wnt signaling is central to a number of brain pathologies. We review here, the significance of this pathway focused in the contribution of the most frequent alterations in receptors, secretable modulators and downstream targets in Alzheimer's disease (AD) and Glioblastoma (GBM). β-catenin and GSK3 levels are pivotal in the neurodegeneration associated to AD contributing to memory deficits, tau phosphorylation, increased β-amyloid production and modulation of Apolipoprotein E in the brain...
June 21, 2017: Journal of Neurogenetics
https://www.readbyqxmd.com/read/28622009/mir-139-5p-represses-bmsc-osteogenesis-via-targeting-wnt-%C3%AE-catenin-signaling-pathway
#2
Haitao Long, Buhua Sun, Liang Cheng, Shushan Zhao, Yong Zhu, Ruibo Zhao, Jianxi Zhu
Osteogenesis of mesenchymal stem cells (MSCs) has played a necessary role in the repair of bone. According to some reports, microRNAs participate in different physiological activity of the cells, including cell differentiation. This study investigated the function that miR-139-5p plays in the osteogenic differentiation of human bone marrow MSCs (hBMSCs). In addition to miR-139-5p, the effects of alkaline phosphatase (ALP), a membrane-bound metalloenzyme that is considered an early osteogenic differentiation marker, have also been investigated...
June 16, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28614361/molecular-cloning-characterization-and-expression-analysis-of-frizzled-6-in-the-small-intestine-of-pigs-sus-scrofa
#3
Lijun Zou, Xiaocheng Wang, Liping Jiang, Shengping Wang, Xia Xiong, Huansheng Yang, Wei Gao, Min Gong, Chien-An A Hu, Yulong Yin
Frizzled 6 (FZD6) encodes an integral membrane protein that functions in multiple signal transduction pathways, for example, as a receptor in Wnt/planar cell polarity (PCP) signaling pathway for polarized cell migration and organ morphogenesis. Mutations in FZD6 have been identified in a variety of tumors. In this study, the full-length cDNA of Sus scrofa FZD6 (Sfz6) was cloned and characterized. Nucleotide sequence analysis demonstrates that the Sfz6 gene encodes the 712 amino-acid (aa) protein with seven transmembrane domain...
2017: PloS One
https://www.readbyqxmd.com/read/28605875/mir-1254-promotes-lung-cancer-cell-proliferation-by-targeting-sfrp1
#4
Hong Li, Tian Yang, Dong Shang, Zhongmin Sun
Lung cancer is the leading cause of cancer deaths worldwide, many miRNAs play critical role in lung cancer initiation and progression. Here, we demonstrated that miR-1254 was upregulated in lung cancer tissues and cells. miR-1254 overexpression promoted lung cancer cell proliferation determined by MTT assay, colony formation assay, soft agar growth ability assay and BrdU incorporation assay, miR-1254 knockdown suppressed lung cancer cell proliferation. Mechanism analysis revealed that Wnt/β-catenin pathway antagonist secreted frizzled related protein 1 (SFRP1) was its target, its expression was opposite to SFRP1 level, and directly bound to the 3'UTR of SFRP1...
June 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28596769/c1-complex-an-adaptable-proteolytic-module-for-complement-and-non-complement-functions
#5
REVIEW
Jinhua Lu, Uday Kishore
Complement C1 is the defining component of the classical pathway. Within the C1qC1r2C1s2 complex, C1q functions as a molecular scaffold for C1r2C1s2 and C1q binding to its ligands activates these two serine proteases. The classic C1q ligands are antigen-bound antibodies and activated C1s cleaves C4 and C2 to initiate the complement cascade. Recent studies suggest broad C1 functions beyond the complement system. C1q binds to the Frizzled receptors to activate C1s, which cleaves lipoprotein receptor-related protein 6 to trigger aging-associated Wnt receptor signaling...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28589318/matricellular-proteins-in-cancer-a-focus-on-secreted-frizzled-related-proteins
#6
Krista Marie Vincent, Lynne-Marie Postovit
Tumours are complex entities, wherein cancer cells interact with myriad soluble, insoluble and cell associated factors. These microenvironmental mediators regulate tumour growth, progression and metastasis, and are produced by cancer cells and by stromal components such as fibroblast, adipocytes and immune cells. Through their ability to bind to extracellular matrix proteins, cell surface receptors and growth factors, matricellular proteins enable a dynamic reciprocity between cancer cells and their microenvironment...
June 7, 2017: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/28576860/coordination-of-heparan-sulfate-proteoglycans-with-wnt-signaling-to-control-cellular-migrations-and-positioning-in-caenorhabditis-elegans
#7
Kristian Saied-Santiago, Robert A Townley, John D Attonito, Dayse S da Cunha, Carlos A Diaz-Balzac, Eillen Tecle, Hannes E Bülow
Heparan sulfates are linear polysaccharides with complex modification patterns, which are covalently bound via conserved attachment sites to core proteins to form heparan sulfate proteoglycans (HSPGs). HSPGs regulate many aspects of the development and function of the nervous system, including cell migration, morphology, and network connectivity. HSPGs function as co-factors for multiple signaling pathways, including the Wnt signaling molecules and their Frizzled receptors. To investigate the functional interactions among the HSPG and Wnt networks, we conducted genetic analyses of each, and also between these networks using five cellular migrations in the nematode Caenorhabditis elegans We find that HSPG core proteins act genetically in a combinatorial fashion dependent on the cellular contexts...
June 2, 2017: Genetics
https://www.readbyqxmd.com/read/28573495/rnf43-is-mutated-less-frequently-in-lynch-syndrome-compared-with-sporadic-microsatellite-unstable-colorectal-cancers
#8
Lochlan J Fennell, Mark Clendenning, Diane M McKeone, Saara H Jamieson, Samanthy Balachandran, Jennifer Borowsky, John Liu, Futoshi Kawamata, Catherine E Bond, Christophe Rosty, Matthew E Burge, Daniel D Buchanan, Barbara A Leggett, Vicki L J Whitehall
The WNT signaling pathway is commonly altered during colorectal cancer development. The E3 ubiquitin ligase, RNF43, negatively regulates the WNT signal through increased ubiquitination and subsequent degradation of the Frizzled receptor. RNF43 has recently been reported to harbor frequent truncating frameshift mutations in sporadic microsatellite unstable (MSI) colorectal cancers. This study assesses the relative frequency of RNF43 mutations in hereditary colorectal cancers arising in the setting of Lynch syndrome...
June 1, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28565807/arsenic-trioxide-increases-expression-of-secreted-frizzled-related-protein-1-gene-and-inhibits-the-wnt-%C3%AE-catenin-signaling-pathway-in-jurkat-cells
#9
Yan Wang, Zunsong Wang, Hong Li, Wenwei Xu, Lin Dong, Yan Guo, Saran Feng, Kehong Bi, Chuansheng Zhu
The aim of the present study was to investigate the demethylation effect of arsenic trioxide (As2O3) on the secreted frizzled-related protein 1 (SFRP1) gene and its ability to inhibit the Wingless-type MMTV integration site family (WNT) pathway in Jurkat cells. Methylation-specific polymerase chain reaction was used to examine the CpG island methylation status of the SFRP1 gene in leukemia cell lines. In addition, the effects on Jurkat cells of treatment with different concentrations of As2O3 for 48 h were investigated...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28560804/wnt-is-necessary-for-mesenchymal-to-epithelial-transition-in-colorectal-cancer-cells
#10
Renate H M Schwab, Nancy Amin, Dustin J Flanagan, Timothy M Johanson, Toby J Phesse, Elizabeth Vincan
BACKGROUND: Metastasis underlies most colorectal cancer mortality. Cancer cells spread through the body as single cells or small clusters of cells that have an invasive, mesenchymal, non-proliferative phenotype. At the secondary site, they revert to a proliferative 'tumor constructing' epithelial phenotype to rebuild a tumor. We previously developed a unique in vitro 3D model, called LIM1863-Mph, which faithfully recapitulates these reversible transitions that underpin colorectal cancer metastasis...
May 30, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28546512/wnt5a-promotes-frizzled-4-signalosome-assembly-by-stabilizing-cysteine-rich-domain-dimerization
#11
Zachary J DeBruine, Jiyuan Ke, Kaleeckal G Harikumar, Xin Gu, Peter Borowsky, Bart O Williams, Wenqing Xu, Laurence J Miller, H Eric Xu, Karsten Melcher
Wnt/β-catenin signaling is activated when extracellular Wnt ligands bind Frizzled (FZD) receptors at the cell membrane. Wnts bind FZD cysteine-rich domains (CRDs) with high affinity through a palmitoylated N-terminal "thumb" and a disulfide-stabilized C-terminal "index finger," yet how these binding events trigger receptor activation and intracellular signaling remains unclear. Here we report the crystal structure of the Frizzled-4 (FZD4) CRD in complex with palmitoleic acid, which reveals a CRD tetramer consisting of two cross-braced CRD dimers...
May 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28536422/secreted-frizzled-related-protein-4-sfrp4-chemo-sensitizes-cancer-stem-cells-derived-from-human-breast-prostate-and-ovary-tumor-cell-lines
#12
A Deshmukh, S Kumar, F Arfuso, P Newsholme, A Dharmarajan
This study investigated molecular signals essential to sustain cancer stem cells (CSCs) and assessed their activity in the presence of secreted frizzled-related protein 4 (sFRP4) alone or in combination with chemotherapeutic drugs. SFRP4 is a known Wnt antagonist, and is also pro-apoptotic and anti-angiogenic. Additionally, sFRP4 has been demonstrated to confer chemo-sensitization and improve chemotherapeutic efficacy. CSCs were isolated from breast, prostate, and ovary tumor cell lines, and characterized using tumor-specific markers such as CD44(+)/CD24(-)/CD133(+)...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28534940/the-wnt-regulator-sfrp4-inhibits-mesothelioma-cell-proliferation-migration-and-antagonizes-wnt3a-via-its-netrin-like-domain
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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