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https://www.readbyqxmd.com/read/28704799/microrna-539-inhibits-glioma-cell-proliferation-and-invasion-by-targeting-dixdc1
#1
Junjie Quan, Jianqiang Qu, Le Zhou
Dysregulation of microRNAs (miRNAs) has been suggested to contribute to malignant progression of glioma. Previous studies have demonstrated that miR-539 is dysregulated in malignant progression of cancers. However, the potential role and mechanism of miR-539 in the progression of glioma remains unclear. In this study, we aimed to investigate the expression status and functional significance of miR-539 in glioma. We found that miR-539 expression was significantly decreased in glioma cell lines and tissues. Overexpression of miR-539 markedly inhibited glioma cell proliferation and invasion, while miR-539 suppression exhibited the opposite effect...
July 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28703283/wnt-signaling-pathways-in-chronic-lymphocytic-leukemia-and-b-cell-lymphomas
#2
REVIEW
Pavlína Janovská, Vítězslav Bryja
In this review, we discuss the intricate roles of the WNT signaling network in the development and progression of mature B cell-derived hematological malignancies, with a focus on chronic lymphocytic leukemia (CLL) and related B cell lymphomas. We review the current literature and highlight the differences between the β-catenin-dependent and independent branches of WNT signaling. Special attention is paid to the role of the non-canonical WNT/Planar cell polarity (PCP) pathway, mediated by the WNT5-ROR1-Dishevelled (DVL) signaling axis in CLL...
July 12, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28701694/defective-cftr-leads-to-aberrant-%C3%AE-catenin-activation-and-kidney-fibrosis
#3
Jie Ting Zhang, Yan Wang, Jun Jiang Chen, Xiao Hu Zhang, Jian Da Dong, Lai Ling Tsang, Xiao Ru Huang, Zhiming Cai, Hui Yao Lan, Xiao Hua Jiang, Hsiao Chang Chan
Cystic fibrosis transmembrane conductance regulator (CFTR), known as a cAMP-activated Cl(-) channel, is widely expressed at the apical membrane of epithelial cells in a wide variety of tissues. Of note, despite the abundant expression of CFTR in mammalian kidney, the role of CFTR in kidney disease development is unclear. Here, we report that CFTR expression is downregulated in the UUO (unilateral ureteral obstruction)-induced kidney fibrosis mouse model and human fibrotic kidneys. Dysfunction or downregulation of CFTR in renal epithelial cells leads to alteration of genes involved in Epithelial-Mesenchymal Transition (EMT) and kidney fibrosis...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28682694/daam1-regulates-fascin-for-actin-assembly-in-mouse-oocyte-meiosis
#4
Yujie Lu, Yu Zhang, Meng-Hao Pan, Nam-Hyung Kim, Shao-Chen Sun, Xiang-Shun Cui
As a formin protein, Daam1 (Dishevelled-associated activator of morphogenesis 1) is reported to regulate series of cell processes like endocytosis, cell morphology and migration via its effects on actin assembly in mitosis. However, whether Daam1 plays roles in female meiosis remains uncertain. In this study, we investigated the expression and functions of Daam1 during mouse oocyte meiosis. Our results indicated that Daam1 localized at the cortex of oocytes, which was similar with actin filaments. After Daam1 morpholino (MO) microinjection, the expression of Daam1 significantly decreased, which resulted in the failure of oocyte polar body extrusion...
July 6, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28679628/recruitment-of-epac2a-to-insulin-granule-docking-sites-regulates-priming-for-exocytosis
#5
Ida Alenkvist, Nikhil R Gandasi, Sebastian Barg, Anders Tengholm
Epac is a cAMP-activated guanine nucleotide exchange factor that mediates cAMP signaling in various types of cells, including β-cells, where it is involved in the control of insulin secretion. Upon activation, the protein redistributes to the plasma membrane but the underlying molecular mechanisms and functional consequences are unclear. Using quantitative high-resolution microscopy we found that cAMP elevation caused rapid binding of Epac2A to the β-cell plasma membrane, where it accumulated specifically at secretory granules and rendered them more prone to undergo exocytosis...
July 5, 2017: Diabetes
https://www.readbyqxmd.com/read/28674183/n-terminal-part-of-dishevelled-dep-domain-is-required-for-wnt-%C3%AE-catenin-signaling-in-mammalian-cells
#6
Petra Paclíková, Ondřej Bernatík, Tomasz Witold Radaszkiewicz, Vítězslav Bryja
Dishevelled (DVL) proteins are key mediators of Wnt/β-catenin signaling pathway. All DVL proteins contain three conserved domains -- DIX, PDZ and DEP. There is a consensus in the field that DIX domain is critical for Wnt/β-catenin signaling but contradictory evidence exists regarding the function of the DEP domain. It has been difficult until recently to test the importance of the DEP domain rigorously because of the interference with endogenous DVL, expressed in all Wnt-responsive cell lines. In this study, we took advantage of DVL KO (DVL1/DVL2/DVL3-triple knockout) cells, fully deficient in Wnt3a-induced signaling events, and performed series of rescue experiments...
July 3, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28668722/the-tyrosine-y250-2-39-in-frizzled-4-defines-a-conserved-motif-important-for-structural-integrity-of-the-receptor-and-recruitment-of-disheveled
#7
Katerina Strakova, Pierre Matricon, Chika Yokota, Elisa Arthofer, Ondrej Bernatik, David Rodriguez, Ernest Arenas, Jens Carlsson, Vitezslav Bryja, Gunnar Schulte
Frizzleds (FZDs) are unconventional G protein-coupled receptors, which activate diverse intracellular signaling pathways via the phosphoprotein Disheveled (DVL) and heterotrimeric G proteins. The interaction interplay of FZDs with DVL and G proteins is complex, involves different regions of FZD and the potential dynamics are poorly understood. In the present study, we aimed to characterize the function of a highly conserved tyrosine (Y250(2.39)) in the intracellular loop 1 (IL1) of human FZD4. We have found Y250(2...
June 29, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28665270/meru-couples-planar-cell-polarity-with-apical-basal-polarity-during-asymmetric-cell-division
#8
Jennifer J Banerjee, Birgit L Aerne, Maxine V Holder, Simon Hauri, Matthias Gstaiger, Nicolas Tapon
Polarity is a shared feature of most cells. In epithelia, apical-basal polarity often coexists, and sometimes intersects with planar cell polarity (PCP), which orients cells in the epithelial plane. From a limited set of core building blocks (e.g. the Par complexes for apical-basal polarity and the Frizzled/Dishevelled complex for PCP), a diverse array of polarized cells and tissues are generated. This suggests the existence of little-studied tissue-specific factors that rewire the core polarity modules to the appropriate conformation...
June 30, 2017: ELife
https://www.readbyqxmd.com/read/28650466/ror2-mediated-alternative-wnt-signaling-regulates-cell-fate-and-adhesion-during-mammary-tumor-progression
#9
K Roarty, A D Pfefferle, C J Creighton, C M Perou, J M Rosen
Cellular heterogeneity is a common feature in breast cancer, yet an understanding of the coexistence and regulation of various tumor cell subpopulations remains a significant challenge in cancer biology. In the current study, we approached tumor cell heterogeneity from the perspective of Wnt pathway biology to address how different modes of Wnt signaling shape the behaviors of diverse cell populations within a heterogeneous tumor landscape. Using a syngeneic TP53-null mouse model of breast cancer, we identified distinctions in the topology of canonical Wnt β-catenin-dependent signaling activity and non-canonical β-catenin-independent Ror2-mediated Wnt signaling across subtypes and within tumor cell subpopulations in vivo...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28642367/the-activities-of-the-c-terminal-regions-of-the-formin-protein-disheveled-associated-activator-of-morphogenesis-daam-in-actin-dynamics
#10
Andrea Teréz Vig, István Földi, Szilárd Szikora, Ede Migh, Rita Gombos, Mónika Ágnes Tóth, Tamás Huber, Réka Pintér, Gábor Csaba Talián, József Mihály, Beáta Bugyi
Disheveled-associated activator of morphogenesis (DAAM) is a diaphanous-related formin protein essential for the regulation of actin cytoskeleton dynamics in diverse biological processes. The conserved formin homology 1 and 2 (FH1-FH2) domains of DAAM catalyze actin nucleation and processively mediate filament elongation. These activities are indirectly regulated by the N-, and C-terminal regions flanking the FH1-FH2 domains. Recently, the C-terminal diaphanous-autoregulatory domain (DAD) and the C-terminus (CT) of formins have also been shown to regulate actin assembly by directly interacting with actin...
June 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28618949/iq-domain-gtpase-activating-protein-1-promotes-the-malignant-phenotype-of-invasive-ductal-breast-carcinoma-via-canonical-wnt-pathway
#11
Huan-Yu Zhao, Yang Han, Jian Wang, Lian-He Yang, Xiao-Ying Zheng, Jiang Du, Guang-Ping Wu, En-Hua Wang
IQ-domain GTPase-activating protein 1 is a scaffolding protein with multidomain which plays a role in modulating dishevelled (Dvl) nuclear translocation in canonical Wnt pathway. However, the biological function and mechanism of IQ-domain GTPase-activating protein 1 in invasive ductal carcinoma (IDC) remain unknown. In this study, we found that IQ-domain GTPase-activating protein 1 expression was elevated in invasive ductal carcinoma, which was positively correlated with tumor grade, lymphatic metastasis, and poor prognosis...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28603713/dishevelled-paralogs-in-vertebrate-development-redundant-or-distinct
#12
REVIEW
Marc Gentzel, Alexandra Schambony
Dishevelled (DVL) proteins are highly conserved in the animal kingdom and are important key players in β-Catenin-dependent and -independent Wnt signaling pathways. Vertebrate genomes typically comprise three DVL genes, DVL1, DVL2, and DVL3. Expression patterns and developmental functions of the three vertebrate DVL proteins however, are only partially redundant in any given species. Moreover, expression and function of DVL isoforms have diverged between different vertebrate species. All DVL proteins share basic functionality in Wnt signal transduction...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28595998/targeting-of-cxxc5-by-a-competing-peptide-stimulates-hair-re-growth-and-wound-induced-hair-neogenesis
#13
Soung-Hoon Lee, Seol Hwa Seo, Dong-Hwan Lee, Long-Quan Pi, Won-Soo Lee, Kang-Yell Choi
The Wnt/β-catenin pathway has been implicated in hair follicle development and hair regeneration in adults. We discovered that CXXC-type zinc finger protein 5 (CXXC5) is a negative regulator of the Wnt/β-catenin pathway involved in hair re-growth and wound-induced hair follicle neogenesis (WIHN) via an interaction with Dishevelled (Dvl). CXXC5 was up-regulated in miniaturized hair follicles and arrector pili muscles in human balding scalps. The inhibitory effects of CXXC5 on alkaline phosphatase activity and cell proliferation were demonstrated using human hair follicle dermal papilla cells...
June 5, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28589433/overexpression-of-dishevelled-2-is-involved-in-tumor-metastasis-and-is-associated-with-poor-prognosis-in-hepatocellular-carcinoma
#14
C Zhang, C Li, X Chen, Y Zhou, B Yin, R Ni, Y Zhang, J Liu
PURPOSE: Although hepatocellular carcinoma (HCC) is one of the most common malignant tumors, its molecular mechanism is still unknown. Dishevelled 2 (Dvl2) is one of the downstream targets of non-canonical Wnt signaling, which has been demonstrated to be of great importance in the progression of cancers. Nevertheless, the expression mechanisms and physiological significance of Dvl2 in HCC remain unclear. METHODS: Western blotting and immunohistochemistry were used to measure Dvl2 protein expression in HCC and adjacent normal tissues of 101 patients...
June 6, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28548684/origins-of-anterior-posterior-polarity-by-localized-activation-of-disheveled
#15
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/28546512/wnt5a-promotes-frizzled-4-signalosome-assembly-by-stabilizing-cysteine-rich-domain-dimerization
#16
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/28543074/wwc3-regulates-the-wnt-and-hippo-pathways-via-dishevelled-proteins-and-large-tumour-suppressor-1-to-suppress-lung-cancer-invasion-and-metastasis
#17
Qiang Han, Xuyong Lin, Xiupeng Zhang, Guiyang Jiang, Yong Zhang, Yuan Miao, Xuezhu Rong, Xiaoying Zheng, Yong Han, Xu Han, Jingjing Wu, Joachim Kremerskothen, Enhua Wang
The scaffolding protein WWC (WW and C2-domain containing) family is known to regulate cell proliferation and organ size via the Hippo signalling pathway. However, the expression level of WWC3 in human tumours and the mechanisms underlying its role in cellular signal transduction have not yet been reported. Herein, we explored the potential roles of WWC3 in lung cancer cells and the corresponding molecular mechanisms. We found low WWC3 expression in both lung cancer cell lines and lung cancer specimens, which was associated with low differentiation, advanced pTNM stage, positive lymph node metastasis, and poor prognosis in patients with lung cancer...
May 25, 2017: Journal of Pathology
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
#18
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/28513833/potential-role-and-prognostic-importance-of-dishevelled-2-in-epithelial-ovarian-cancer
#19
Rong Liu, Jialin Cheng, Yannan Chen, Wei Wang, Jie Chen, Guoxin Mao
OBJECTIVE: To investigate the role and prognostic importance of Dvl2 in human epithelial ovarian cancer (EOC). METHODS: A multimethod study was undertaken including patients with pathologically confirmed non-metastatic EOC who underwent surgery for maximum tumor resection at a center in China. Dvl2 expression was assessed by western blot using fresh EOC tissues and normal ovarian tissues obtained between June 2014 and January 2015. Additionally, retrospective data were obtained for patients treated between April 2004 and September 2009...
May 17, 2017: International Journal of Gynaecology and Obstetrics
https://www.readbyqxmd.com/read/28506997/the-phosphatase-pgam5-antagonizes-wnt-%C3%AE-catenin-signaling-in-embryonic-anterior-posterior-axis-patterning
#20
Verena Rauschenberger, Dominic B Bernkopf, Sabrina Krenn, Kowcee Jalal, Jens Heller, Jürgen Behrens, Marc Gentzel, Alexandra Schambony
The scaffold protein Dishevelled is a central intracellular component of Wnt signaling pathways. Various kinases have been described that regulate and modulate Wnt signaling through phosphorylation of Dishevelled. However, besides general protein phosphatases 1 and 2 (PP1 and PP2), no specific protein phosphatases have been identified. Here, we report on the identification and functional characterization of the protein phosphatase Pgam5 in vitro and in vivo in Xenopus Pgam5 is a novel antagonist of Wnt/β-Catenin signaling in human cells and Xenopus embryogenesis...
June 15, 2017: Development
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