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Dishevelled

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https://www.readbyqxmd.com/read/28543074/wwc3-regulates-the-wnt-and-hippo-pathways-via-dvls-and-lats1-to-suppress-lung-cancer-invasion-and-metastasis
#1
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 p-TNM 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
#2
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
#3
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
#4
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 the 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 Pgam5 is a novel antagonist of Wnt/β-Catenin signaling in human cells and Xenopus embryogenesis...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28481871/suppression-of-planar-cell-polarity-signaling-and-migration-in-glioblastoma-by-nrdp1-mediated-dvl-polyubiquitination
#5
J H Wald, J Hatakeyama, I Printsev, A Cuevas, W H D Fry, M J Saldana, K VanderVorst, A Rowson-Hodel, J M Angelastro, C Sweeney, K L Carraway Rd
The lethality of the aggressive brain tumor glioblastoma multiforme (GBM) results in part from its strong propensity to invade surrounding normal brain tissue. Although oncogenic drivers such as epidermal growth factor receptor activation and Phosphatase and Tensin homolog inactivation are thought to promote the motility and invasiveness of GBM cells via phosphatidylinostitol 3-kinase activation, other unexplored mechanisms may also contribute to malignancy. Here we demonstrate that several components of the planar cell polarity (PCP) arm of non-canonical Wnt signaling including VANGL1, VANGL2 and FZD7 are transcriptionally upregulated in glioma and correlate with poorer patient outcome...
May 8, 2017: Oncogene
https://www.readbyqxmd.com/read/28463110/the-sec14-like-phosphatidylinositol-transfer-proteins-sec14l3-sec14l2-act-as-gtpase-proteins-to-mediate-wnt-ca-2-signaling
#6
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/28455968/dishevelled-3-phosphorylation-is-governed-by-hipk2-pp1c%C3%AE-itch-axis-and-the-non-phosphorylated-form-promotes-cancer-stemness-via-lgr5-in-hepatocellular-carcinoma
#7
Yu-Man Tsui, Karen Man-Fong Sze, Edmund Kwok-Kwan Tung, Daniel Wai-Hung Ho, Terence Kin-Wah Lee, Irene Oi-Lin Ng
Dishevelled-3 (Dvl3) is regarded as a binding hub with many different interacting partners. However, its regulation and mechanism on cancer stemness remain to be explored. In this study, we showed that Dvl3 was significantly overexpressed in human hepatocellular carcinomas (HCCs) and promoted cancer stemness both in vitro and in vivo. We found that the non-phosphorylated (NP)-Dvl3 was more stable than the phosphorylated form, more active in activating β-catenin transcriptional activity, and more potent in enhancing self-renewal ability in HCC cells...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28447744/cyclic-compression-stimulates-osteoblast-differentiation-via-activation-of-the-wnt-%C3%AE-catenin-signaling-pathway
#8
Xi Chen, Jianmin Guo, Yu Yuan, Zhongguang Sun, Binglin Chen, Xiaoyang Tong, Lingli Zhang, Chao Shen, Jun Zou
It is widely accepted that mechanical stress is an important factor in bone associated cell differentiation, including that of mesenchymal stem cells, osteoblasts and osteocytes. The present study aimed to determine the effect of mechanical cyclic compressive load on osteoblast differentiation, and whether this was associated with activation of the wingless‑type (Wnt)/β-catenin signaling pathway. Using a 3D scaffold model, MC3T3‑E1 cells were exposed to cyclic compressive loading via the Flexcell‑5000C™ Compression system...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28418856/low-density-lipoprotein-receptor-related-protein-6-is-a-novel-coreceptor-of-protease-activated-receptor-2-in-the-dynamics-of-cancer-associated-%C3%AE-catenin-stabilization
#9
Jeetendra Kumar Nag, Arun Kancharla, Myriam Maoz, Hagit Turm, Daniel Agranovich, Chhedi Lal Gupta, Beatrice Uziely, Rachel Bar-Shavit
Protease-activated receptor-2 (PAR2) plays a central role in cancer; however, the molecular machinery of PAR2-instigated tumors remains to be elucidated. We show that PAR2 is a potent inducer of β-catenin stabilization, a core process in cancer biology, leading to its transcriptional activity. Novel association of low-density lipoprotein-related protein 6 (LRP6), a known coreceptor of Frizzleds (Fz), with PAR2 takes place following PAR2 activation. The association between PAR2 and LRP6 was demonstrated employing co-immunoprecipitation, bioluminescence resonance energy transfer (BRET), and confocal microscopy analysis...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28406046/depdc5-as-a-potential-therapeutic-target-for-epilepsy
#10
Kenneth A Myers, Ingrid E Scheffer
Dishevelled, Egl-10 and Pleckstrin (DEP) domain-containing protein 5 (DEPDC5) is a protein subunit of the GTPase-activating proteins towards Rags 1 (GATOR1) complex. GATOR1 is a recently identified modulator of mechanistic target of rapamycin (mTOR) activity. mTOR is a key regulator of cell proliferation and metabolism; disruption of the mTOR pathway is implicated in focal epilepsy, both acquired and genetic. Tuberous sclerosis is the prototypic mTOR genetic syndrome with epilepsy, however GATOR1 gene mutations have recently been shown to cause lesional and non-lesional focal epilepsy...
April 13, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28366812/dishevelled-stability-is-positively-regulated-by-pkc%C3%AE-mediated-phosphorylation-induced-by-wnt-agonists
#11
Dora M Velázquez, M Cristina Castañeda-Patlán, Martha Robles-Flores
Dishevelled (Dvl) proteins are central mediators of both canonical and non-canonical Wnt signaling. It is well known that, upon Wnt stimulation, Dvl becomes phosphorylated. However, how Wnt-induced phosphorylation of Dvl is regulated and its consequences are poorly understood. Here we found that Dvl proteins are overexpressed in colon cancer cells. In addition, we found that Wnt3a treatment rapidly induces hyperphosphorylation and stabilization of Dvl2 and Dvl3. The latter can be blocked by inhibition of Protein Kinase C (PKC)α, PKCδ, and PKCζ isoforms...
March 31, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28334810/bimodal-regulation-of-dishevelled-function-by-vangl2-during-morphogenesis
#12
Hwa-Seon Seo, Raymond Habas, Chenbei Chang, Jianbo Wang
Convergent extension (CE) is a fundamental morphogenetic mechanism that underlies numerous processes in vertebrate development, and its disruption can lead to human congenital disorders such as neural tube closure defects. The dynamic, oriented cell intercalation during CE is regulated by a group of core proteins identified originally in flies to coordinate epithelial planar cell polarity (PCP). The existing model explains how core PCP proteins, including Van Gogh (Vang) and Dishevelled (Dvl), segregate into distinct complexes on opposing cell cortex to coordinate polarity among static epithelial cells...
June 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28289771/coherent-array-of-branched-filamentary-scales-along-the-wing-margin-of-a-small-moth
#13
Akihiro Yoshida, Shin Tejima, Masayuki Sakuma, Yositaka Sakamaki, Ryuji Kodama
In butterflies and moths, the wing margins are fringed with specialized scales that are typically longer than common scales. In the hindwings of some small moths, the posterior margins are fringed with particularly long filamentary scales. Despite the small size of these moth wings, these scales are much longer than those of large moths and butterflies. In the current study, photography of the tethered flight of a small moth, Phthorimaea operculella, revealed a wide array composed of a large number of long filamentary scales...
April 2017: Die Naturwissenschaften
https://www.readbyqxmd.com/read/28288669/implication-of-overexpression-of-dishevelled-associated-activator-of-morphogenesis-1-daam-1-for-the-pathogenesis-of-human-idiopathic-pulmonary-arterial-hypertension-ipah
#14
Shun Yanai, Megumi Wakayama, Haruo Nakayama, Minoru Shinozaki, Hisayuki Tsukuma, Naobumi Tochigi, Tetsuo Nemoto, Tsutomu Saji, Kazutoshi Shibuya
BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a rare, fatal disease of unknown pathogenesis. Evidence from our recent study suggests that IPAH pathogenesis is related to upregulation of the Wnt/planar cell polarity (Wnt/PCP) pathway. We used microscopic observation and immunohistochemical techniques to identify expression patterns of cascading proteins-namely Wnt-11, dishevelled-2 (Dvl-2), and dishevelled-associated activator of morphogenesis 1 (Daam-1)-in pulmonary arteries...
March 14, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28258110/planar-cell-polarity-effector-fritz-interacts-with-dishevelled-and-has-multiple-functions-in-regulating-pcp
#15
Ying Wang, Victor F Naturale, Paul N Adler
The Planar cell Polarity Effector (PPE) genes inturned, fuzzy, and fritz are downstream components in the frizzled/starry night signaling pathway, and their function is instructed by upstream Planar Cell Polarity (PCP) core genes such as frizzled and dishevelled PPE proteins accumulate asymmetrically in wing cells and function in a protein complex mediated by direct interactions between In and Frtz and In and Fy. How the PCP proteins instruct the accumulation of PPE protein is unknown. We found a likely direct interaction between Dishevelled and Fritz and Dishevelled and Fuzzy that could play a role in this...
April 3, 2017: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28223363/autoinhibition-of-dishevelled-protein-regulated-by-its-extreme-c-terminus-plays-a-distinct-role-in-wnt-%C3%AE-catenin-and-wnt-planar-cell-polarity-pcp-signaling-pathways
#16
Jing Qi, Ho-Jin Lee, Audrey Saquet, Xiao-Ning Cheng, Ming Shao, Jie J Zheng, De-Li Shi
Dishevelled (Dvl) is a key intracellular signaling molecule that mediates the activation of divergent Wnt pathways. It contains three highly conserved domains known as DIX, PDZ, and DEP, the functions of which have been well characterized in β-catenin-dependent canonical and β-catenin-independent noncanonical Wnt signaling. The C-terminal region is also highly conserved from invertebrates to vertebrates. However, its function in regulating the activation of different Wnt signals remains unclear. We reported previously that Dvl conformational change triggered by the highly conserved PDZ-binding C terminus is important for the pathway specificity...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28187436/dishevelled2-promotes-apoptosis-and-inhibits-inflammatory-cytokine-secretion-in-rheumatoid-arthritis-fibroblast-like-synoviocytes-through-crosstalk-with-the-nf-%C3%AE%C2%BAb-pathway
#17
Xing Zhen Liu, Jie Fan, Ke Qi, Shu Peng Liu, Wei Dong Xu, Ying Gao, Xiao Dan Gu, Jia Li, Chen Guang Bai, Ye Qing Shi, Lan Ling Zhang, Dong Bao Zhao
Dishevelled (Dvl) not only links the canonical Wnt and non-canonical Wnt pathways but can also crosstalk with other pathways. As there is no systematic study to date on Dvl in rheumatoid arthritis (RA), we explored the impact of Dvl2 on proliferation and inflammatory cytokine secretion in RA fibroblast-like synoviocytes (FLSs). Expression of Dvl2 in RA synovial tissue and RA-FLSs was measured. Dvl2 was overexpressed in collagen-induced arthritis rats and human RA-FLSs,. the apoptosis and secretion of inflammatory cytokines were observed...
February 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28181235/new-advances-of-tmem88-in-cancer-initiation-and-progression-with-special-emphasis-on-wnt-signaling-pathway
#18
REVIEW
Yun-Xuan Ge, Chang-Hui Wang, Fu-Yong Hu, Lin-Xin Pan, Jie Min, Kai-Yuan Niu, Lei Zhang, Jun Li, Tao Xu
Transmembrane protein 88 (TMEM88), a newly discovered protein localized on the cell membrane. Recent studies showed that TMEM88 was involved in the regulation of several types of cancer. TMEM88 was expressed at significantly higher levels in breast cancer (BC) cell line than in normal breast cell line with co-localized with Dishevelled (DVL) in the cytoplasm of BC cell line. TMEM88 silencing in the ovarian cancer cell line CP70 resulted in significant upregulation of Wnt downstream genes (c-Myc, cyclin-D1) and other Wnt target genes including JUN, PTIX2, CTNNB1 (β-catenin), further supporting that TMEM88 inhibits canonical Wnt signaling pathway...
February 9, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28173817/pigment-epithelium-derived-factor-alleviates-endothelial-injury-by-inhibiting-wnt-%C3%AE-catenin-pathway
#19
Shouyuan Ma, Shutong Yao, Hua Tian, Peng Jiao, Nana Yang, Ping Zhu, Shucun Qin
BACKGROUND: Oxidized low-density lipoprotein (ox-LDL) can induce endothelial injury and plays a vital role in the procession and development of atherosclerosis. Little is known regarding whether Wnt/β-catenin pathway is involved in ox-LDL-induced endothelial injury or whether it further promotes atherosclerosis via increased oxidative stress. This study aimed to investigate the role of Wnt/β-catenin pathway in ox-LDL-induced vascular endothelial injury and determine whether pigment epithelium-derived factor (PEDF) could alleviate ox-LDL-induced endothelial injury by inhibiting Wnt/β-catenin pathway...
February 7, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28170089/depdc5-mutations-in-familial-and-sporadic-focal-epilepsy
#20
M-H Tsai, C-K Chan, Y-C Chang, Y-T Yu, S-T Chuang, W-L Fan, S-C Li, T-Y Fu, W-N Chang, C-W Liou, Y-C Chuang, C-C Ng, D-Y Hwang, K-S Lim
BACKGROUND AND AIMS: Mutations in the disheveled, Egl-10 and pleckstrin domain-containing protein 5 (DEPDC5) gene have emerged as an important cause of various familial focal epilepsy syndromes. However, the significance of DEPDC5 mutations in patients with sporadic focal epilepsy has yet to be characterized. MATERIALS AND METHODS: We studied a kindred of familial focal epilepsy with variable foci using whole-exome sequencing. We subsequently studied a cohort of 293 patients with focal epilepsy and sequenced all exons of DEPDC5 using targeted resequencing...
February 7, 2017: Clinical Genetics
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