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Dishevelled

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https://www.readbyqxmd.com/read/29786763/mir-124-promotes-proliferation-and-neural-differentiation-of-neural-stem-cells-through-targeting-dact1-and-activating-wnt-%C3%AE-catenin-pathways
#1
Shujie Jiao, Yaling Liu, Yaobing Yao, Junfang Teng
Neural stem cells (NSCs) are multipotent and undifferentiated cells with the potential to differentiate into neuronal lineages and gliocytes. NSCs have the ability to generate and regenerate the brain, indicating the possibility of cell-based therapies for neurological disorders. miR-124 has been demonstrated as a modulator in the survival, expansion, and differentiation of NSCs. However, the underlying molecular mechanisms of miR-124 in NSC development are still far from being understood. The expressions of miR-124, dishevelled binding antagonist of beta-catenin 1 (DACT1), ki-67, Nestin, β-tubulin III, glial fibrillary acidic protein (GFAP), β-catenin, cyclinD1, and glycogen synthase kinase-3β (GSK-3β) were examined by qRT-PCR or western blot...
May 21, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29752407/integrin-%C3%AE-v%C3%AE-3-associated-daam1-is-essential-for-collagen-induced-invadopodia-extension-and-cell-haptotaxis-in-breast-cancer-cells
#2
Ting Yan, Ailiang Zhang, Fangfang Shi, Fei Chang, Jie Mei, Yongjian Liu, Yichao Zhu
The formin protein dishevelled-associated activator of morphogenesis 1 (DAAM1) polymerizes straight actin filaments and mediates migration of cancer cells. However, how DAAM1 governs cell haptotaxis in response to collagen remains unexplored in breast cancer cells. We hypothesized that DAAM1 mediates invadopodia extension and cell haptotaxis in response to type IV collagen in association with integrin receptors. Using Boyden chamber membranes coated with type IV collagen, we show here that type IV collagen activates both DAAM1 and  Ras homolog family member A (RHOA)  and promotes haptotaxis of MDA-MB-231 and MDA-MB-453 breast cancer cells, a process abolished by treatment with the integrin αvβ3 inhibitor cyclo(-RGDfK)...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29749449/dishevelled%C3%A2-2-modulates-osteogenic-differentiation-of-human-synovial-fibroblasts-in-osteoarthritis
#3
Lihua Zhang, Luan Luan, Yingying Ma
Dishevelled (Dvl)‑2 represents one of the cytoplasmic proteins, which serves as a pivotal hub in signaling intermediates through a number of different signaling pathways associated with the Wnt family. The aim of the present study was to investigate the roles and mechanisms of Dvl‑2 on synovial fibroblasts (SFBs) in osteoarthritis (OA). A Cell Counting kit‑8 (CCK‑8) assay was used to determine cell viability. An alkaline phosphatase (ALP) test kit was used to measure the activity of ALP. Western blot and reverse transcription‑quantitative polymerase chain reaction analysis were used to evaluate the protein and mRNA expression, respectively...
May 4, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29690734/-effect-of-dishevelled-2-on-apoptosis-in-rheumatoid-arthritis-fibroblast-like-synoviocytes-through-inhibiting-jak-stat-pathway
#4
X Z Liu, Y Gao, C H Zhu, K Qi, X Xu, D B Zhao
Objective: To investigate if Dishevelled 2 (DVL2) regulates the apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) via the JAK-STAT pathway. Methods: DVL2 overexpressed lentivirus was transfected into RA-FLS and the apoptosis rate was detected by flow cytometry. The effect of DVL2 on RA-FLS signaling pathway was detected by RNA-seq, and then the key genes were verified by RT-PCR. Results: Compared with the control group, DVL2 significantly increased the apoptosis rate of MH7A (3.2%±2.2% vs 25...
April 17, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29686674/wnt5a-signaling-promotes-defense-against-bacterial-pathogens-by-activating-a-host-autophagy-circuit
#5
Suborno Jati, Suman Kundu, Arijit Chakraborty, Sushil Kumar Mahata, Victor Nizet, Malini Sen
Bacterial pathogens are associated with severe infections (e.g., sepsis) and exacerbation of debilitating conditions such as chronic obstructive pulmonary disease (COPD). The interactions of bacterial pathogens with macrophages, a key component of innate immunity and host defense, are not clearly understood and continue to be intensively studied. Having previously demonstrated a role of Wnt5A signaling in phagocytosis, we proceeded to decipher the connection of Wnt5A signaling with infection by pathogenic bacteria, namely Pseudomonas aeruginosa (PA) and Streptococcus pneumoniae (SP), which are related with the progression of COPD and sepsis...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29675451/cftr-modulates-wnt-%C3%AE-catenin-signaling-and-stem-cell-proliferation-in-murine-intestine
#6
Ashlee M Strubberg, Jinghua Liu, Nancy M Walker, Casey D Stefanski, R John MacLeod, Scott T Magness, Lane L Clarke
Background & Aims: Cystic fibrosis (CF) patients and CF mouse models have increased risk for gastrointestinal tumors. CF mice show augmented intestinal proliferation of unknown etiology and an altered intestinal environment. We examined the role of the cystic fibrosis transmembrane conductance regulator (Cftr) in Wnt/β-catenin signaling, stem cell proliferation, and its functional expression in the active intestinal stem cell (ISC) population. Dysregulation of intracellular pH (pHi ) in CF ISCs was investigated for facilitation of Wnt/β-catenin signaling...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29659741/formin-2-regulates-lysosomal-degradation-of-wnt-associated-%C3%AE-catenin-in-neural-progenitors
#7
Gewei Lian, Anjen Chenn, Victor Ekuta, Sneha Kanaujia, Volney Sheen
Although neural progenitor proliferation along the ventricular zone is regulated by β-catenin through Wnt signaling, the cytoskeletal mechanisms that regulate expression and localization of these proteins are not well understood. Our prior studies have shown that loss of the actin-binding Filamin A (FlnA) and actin-nucleating protein Formin 2 (Fmn2) impairs endocytosis of low-density-lipoprotein-receptor-related protein 6 (Lrp6), thereby disrupting β-catenin activation, resulting in decreased brain size. Here, we report that activated RhoA-GTPase disengages Fmn2 N- to C-terminal binding to promote Fmn2 activation and redistribution into lysosomal vesicles...
April 5, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29627878/discovery-of-a-small-molecule-inhibitor-of-dvl-cxxc5-interaction-by-computational-approaches
#8
Songling Ma, Jiwon Choi, Xuemei Jin, Hyun-Yi Kim, Ji-Hye Yun, Weontae Lee, Kang-Yell Choi, Kyoung Tai No
The Wnt/β-catenin signaling pathway plays a significant role in the control of osteoblastogenesis and bone formation. CXXC finger protein 5 (CXXC5) has been recently identified as a negative feedback regulator of osteoblast differentiation through a specific interaction with Dishevelled (Dvl) protein. It was reported that targeting the Dvl-CXXC5 interaction could be a novel anabolic therapeutic target for osteoporosis. In this study, complex structure of Dvl PDZ domain and CXXC5 peptide was simulated with molecular dynamics (MD)...
April 7, 2018: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/29595002/-disheveled-2-around-the-implant-at-an-early-stage-of-hyperlipidemic-rats
#9
Dong Xiaofei, Wang Hui, Lan Jing
OBJECTIVE: This study aims to investigate the expression of disheveled 2 (Dvl2) around the implant of hyperlipidemic rats at an early stage after the implantation. METHODS: A total of 24 Wistar rats were divided equally into the experimental group fed with high-fat diet group and control group fed with a normal diet. After 8 weeks, the serum lipid levels were detected, and rats received implants in the femur metaphysis. Rats were sacrificed at 1, 3, and 5 days after implantation, and the bones around implants were obtained...
February 1, 2018: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/29583038/dishevelled-1-a-pivotal-positive-regulator-of-the-wnt-signalling-pathway-mediates-5-fluorouracil-resistance-in-hepg2-cells
#10
Yisong Xu, Cheng Zhang, Hui Liang, Shanshuang Hu, Pengkun Li, Linna Liu, Xianglong Duan, Chao Chen, Yani Zhang, Penggao Dai
Acquired resistance to 5-fluorouracil (5-FU) frequently occurs in patients with hepatocellular carcinoma (HCC), the underlying molecular mechanisms of which are poorly understood. The aim of this study was to identify candidate genes and associated signalling pathways that may play a role in developing drug resistance following repeated 5-FU treatments. In this work, we established 5-FU-resistant cells (HepG2/5-FU) using stepwise increasing concentrations of 5-FU in parental HepG2 cells. Using transcriptome sequencing, we found that the expressions of the Wnt signalling genes, including negative regulators (DKK1, DKK3, ZNRF3, RNF43 and APC2) and positive regulators (FZD10 and DVL1), were significantly downregulated and upregulated in HepG2/5-FU cells, respectively, resulting in increased Wnt signalling...
March 27, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29571963/first-evidence-of-daam1-localization-in-mouse-seminal-vesicles-and-its-possible-involvement-during-regulated-exocytosis
#11
Massimo Venditti, Chiara Fasano, Alessandra Santillo, Francesco Aniello, Sergio Minucci
Dishevelled-associated activator of morphogenesis 1 (DAAM1) is a protein belonging to the formin family, which regulates, together with the small GTPase RhoA, the nucleation and the assembly of actin fibres through Wnt-Dishevelled PCP pathway. Its role has been investigated in essential biological processes, such as cell polarity, movement and adhesion during morphogenesis and organogenesis. In this work, we studied the expression of DAAM1 mRNA and protein by PCR and Western blot analyses and its co-localization with actin in adult mouse seminal vesicles by immunofluorescence...
March 20, 2018: Comptes Rendus Biologies
https://www.readbyqxmd.com/read/29564122/potential-signaling-pathways-as-therapeutic-targets-for-overcoming-chemoresistance-in-mucinous-ovarian-cancer
#12
Emiko Niiro, Sachiko Morioka, Kana Iwai, Yuki Yamada, Kenji Ogawa, Naoki Kawahara, Hiroshi Kobayashi
Cases of mucinous ovarian cancer are predominantly resistant to chemotherapies. The present review summarizes current knowledge of the therapeutic potential of targeting the Wingless (WNT) pathway, with particular emphasis on preclinical and clinical studies, for improving the chemoresistance and treatment of mucinous ovarian cancer. A review was conducted of English language literature published between January 2000 and October 2017 that concerned potential signaling pathways associated with the chemoresistance of mucinous ovarian cancer...
March 2018: Biomedical Reports
https://www.readbyqxmd.com/read/29559363/dishevelled-a-masterful-conductor-of-complex-wnt-signals
#13
REVIEW
Monica Sharma, Isabel Castro-Piedras, Glenn E Simmons, Kevin Pruitt
The Dishevelled gene was first identified in Drosophila mutants with disoriented hair and bristle polarity [1-3]. The Dsh gene (Dsh/Dvl, in Drosophila and vertebrates respectively) gained popularity when it was discovered that it plays a key role in segment polarity during early embryonic development in Drosophila [4]. Subsequently, the vertebrate homolog of Dishevelled genes were identified in Xenopus (Xdsh), mice (Dvl1, Dvl2, Dvl3), and in humans (DVL1, DVL2, DVL3) [5-10]. Dishevelled functions as a principal component of Wnt signaling pathway and governs several cellular processes including cell proliferation, survival, migration, differentiation, polarity and stem cell renewal...
March 17, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29549110/head-formation-requires-dishevelled-degradation-that-is-mediated-by-march2-in-concert-with-dapper1
#14
Hyeyoon Lee, Seong-Moon Cheong, Wonhee Han, Youngmu Koo, Saet-Byeol Jo, Gun-Sik Cho, Jae-Seong Yang, Sanguk Kim, Jin-Kwan Han
Dishevelled (Dvl/Dsh) is a key scaffold protein that propagates Wnt signaling essential for embryogenesis and homeostasis. However, whether the antagonism of Wnt signaling that is necessary for vertebrate head formation can be achieved through regulation of Dsh protein stability is unclear. Here, we show that membrane-associated RING-CH2 (March2), a RING-type E3 ubiquitin ligase, antagonizes Wnt signaling by regulating the turnover of Dsh protein via ubiquitin-mediated lysosomal degradation in the prospective head region of Xenopus We further found that March2 acquires regional and functional specificities for head formation from the Dsh-interacting protein Dapper1 (Dpr1)...
April 10, 2018: Development
https://www.readbyqxmd.com/read/29545541/toosendanin-inhibits-adipogenesis-by-activating-wnt-%C3%AE-catenin-signaling
#15
Tian-Xing Chen, Xiao-Ying Cheng, Yun Wang, Wu Yin
Toosendanin (TSN), a triterpenoid extracted from Melia toosendan, has been reported to possess anti-oxidant, anti-inflammatory, anti-allergic, and anti-arthritic activities. However, its anti-adipogenic effect remains unknown. Here, we found that TSN dose-dependently attenuated lipid accumulation in preadipocytes 3T3-L1 as evidenced by Oil Red O staining. TSN also significantly downregulated mRNA and protein levels of adipocytokines (adiponectin and leptin), CCAAT/enhancer binding proteins α (C/EBP-α), peroxisome proliferator-activated receptor γ (PPAR-γ), fatty acid synthase, and acetyl-CoA carboxylase in adipocytes...
March 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29528187/down-regulation-of-dishevelled-2-inhibits-cell-proliferation-and-invasion-in-hepatoblastoma
#16
Siqi Huang, Jing Chen, Ruicheng Tian, Jing Wang, Chenjie Xie, Hongxiang Gao, Yuhua Shan, Jie Hong, Zhen Zhang, Min Xu, Song Gu
BACKGROUND: Hepatoblastoma (HB) is the most common liver cancer found in early childhood. These patients suffer poor outcomes and need novel therapies. An abnormal activation of Wnt signaling is the hallmark of HB tumorigenesis, and its pathway is a potential candidate for a pharmacological intervention. PROCEDURE: Tissue samples of patients with HB were collected for RNA-seq, quantitative real-time PCR, and immunohistochemistry to identify if disheveled-2 (Dvl-2) was a target gene...
March 12, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29487190/convergence-of-wnt-growth-factor-and-heterotrimeric-g-protein-signals-on-the-guanine-nucleotide-exchange-factor-daple
#17
Nicolas Aznar, Jason Ear, Ying Dunkel, Nina Sun, Kendall Satterfield, Fang He, Nicholas A Kalogriopoulos, Inmaculada Lopez-Sanchez, Majid Ghassemian, Debashis Sahoo, Irina Kufareva, Pradipta Ghosh
Cellular proliferation, differentiation, and morphogenesis are shaped by multiple signaling cascades, and their dysregulation plays an integral role in cancer progression. Three cascades that contribute to oncogenic potential are those mediated by Wnt proteins and the receptor Frizzled (FZD), growth factor receptor tyrosine kinases (RTKs), and heterotrimeric G proteins and associated GPCRs. Daple is a guanine nucleotide exchange factor (GEF) for the G protein Gαi Daple also binds to FZD and the Wnt/FZD mediator Dishevelled (Dvl), and it enhances β-catenin-independent Wnt signaling in response to Wnt5a-FZD7 signaling...
February 27, 2018: Science Signaling
https://www.readbyqxmd.com/read/29465811/ck1%C3%AE%C2%B5-and-p120-catenin-control-ror2-function-in-noncanonical-wnt-signaling
#18
Josué Curto, Beatriz Del Valle-Pérez, Aida Villarroel, Guillem Fuertes, Meritxell Vinyoles, Raúl Peña, Antonio García de Herreros, Mireia Duñach
Canonical and noncanonical Wnt pathways share some common elements but differ in the responses they evoke. Similar to Wnt ligands acting through the canonical pathway, Wnts that activate the noncanonical signaling, such as Wnt5a, promote Disheveled (Dvl) phosphorylation and its binding to the Frizzled (Fz) Wnt receptor complex. The protein kinase CK1ε is required for Dvl/Fz association in both canonical and noncanonical signaling. Here we show that differently to its binding to canonical Wnt receptor complex, CK1ε does not require p120-catenin for the association with the Wnt5a co-receptor Ror2...
May 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29449653/cftr-mutation-enhances-dishevelled-degradation-and-results-in-impairment-of-wnt-dependent-hematopoiesis
#19
Huaqin Sun, Yan Wang, Jieting Zhang, Yan Chen, Yanyan Liu, Ziyuan Lin, Mingfeng Liu, Kai Sheng, Huijuan Liao, Kam Sze Tsang, Xiaohu Zhang, Xiaohua Jiang, Wenming Xu, Meng Mao, Hsiao Chang Chan
Mutations of cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis (CF) with a multitude of clinical manifestations. Some CF patients develop clinically significant anemia, suggesting that CFTR may regulate hematopoiesis. Here, we report that cftr mutant zebrafish model exhibits primitive and definitive hematopoietic defects with impaired Wnt signaling. Cftr is found to interact, via its PDZ-binding domain (PDZBD), with Dishevelled (Dvl), a key component of Wnt signaling required for hematopoietic progenitor specification, thus protecting Dvl from Dapper1 (Dpr1)-induced lysosomal degradation...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29445127/cripto-1-contributes-to-stemness-in-hepatocellular-carcinoma-by-stabilizing-dishevelled-3-and-activating-wnt-%C3%AE-catenin-pathway
#20
Regina Cheuk-Lam Lo, Carmen Oi-Ning Leung, Kristy Kwan-Shuen Chan, Daniel Wai-Hung Ho, Chun-Ming Wong, Terence Kin-Wah Lee, Irene Oi-Lin Ng
Identification and characterization of functional molecular targets conferring stemness properties in hepatocellular carcinoma (HCC) offers crucial insights to overcome the major hurdles of tumor recurrence, metastasis and chemoresistance in clinical management. In the current study, we investigated the significance of Cripto-1 in contributing to HCC stemness. Cripto-1 was upregulated in the sorafenib-resistant clones derived from HCC cell lines and patient-derived xenograft that we previously developed, suggesting an association between Cripto-1 and stemness...
February 14, 2018: Cell Death and Differentiation
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