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Dishevelled

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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
#1
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 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28181235/new-advances-of-tmem88-in-cancer-initiation-and-progression-with-special-emphasis-on-wnt-signaling-pathway
#2
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
#3
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
#4
Meng-Han Tsai, Chung-Kin Chan, Ying-Chao Chang, Yu-Tzu Yu, Shu-Ting Chuang, Wen-Lang Fan, Sung-Chou Li, Ting-Ying Fu, Wen-Neng Chang, Chia-Wei Liou, Yao-Chung Chuang, Ching-Ching Ng, Daw-Yang Hwang, Kheng-Seang Lim
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. 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
https://www.readbyqxmd.com/read/28153722/inhibition-of-dixdc1-by-microrna-1271-suppresses-the-proliferation-and-invasion-of-prostate-cancer-cells
#5
Jiateng Zhong, Yufei Liu, Qingli Xu, Jian Yu, Muchun Zhang
Disheveled-Axin domain containing 1 (DIXDC1) is involved in the development and progression of multiple cancers. However, the function significance of DIXDC1 in prostate cancer remains unclear. In this study, we investigated the function of DIXDC1 in prostate cancer and the regulation of DIXDC1 by microRNAs (miRNAs). We found that DIXDC1 was highly expressed in prostate cancer cells. Knockdown of DIXDC1 by small interfering RNAs markedly suppressed proliferation, invasion and Wnt signaling in prostate cancer cells...
January 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28153580/from-planar-cell-polarity-to-ciliogenesis-and-back-the-curious-tale-of-the-ppe-and-cplane-proteins
#6
REVIEW
Paul N Adler, John B Wallingford
Why some genes are more popular than others remains an open question, but one example of this phenomenon involves the genes controlling planar cell polarity (PCP), the polarization of cells within a plane of a tissue. Indeed, the so-called 'core' PCP genes such as dishevelled, frizzled, and prickle have been extensively studied both in animal models and by human genetics. By contrast, other genes that influence PCP signaling have received far less attention. Among the latter are inturned, fuzzy, and fritz, but recent work should bring these once obscure regulators into the limelight...
January 30, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28120389/modulating-the-wnt-signaling-pathway-with-small-molecules
#7
REVIEW
Freddi Huan Tran, Jie J Zheng
Wnt signaling is a critical component during embryonic development and also plays an important role in regulating adult tissue homeostasis. Abnormal activation of Wnt signaling has been implicated in many cancers, while reduced activity of Wnt signaling leads to poor wound healing and structural formations. Thus, extensive efforts have been focused on developing small molecules that have potential to either inhibit or activate the pathway, hoping these molecules can offer leads for novel approaches in treating different human diseases...
January 25, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28107606/dishevelled-segment-polarity-protein-3-dvl3-a-novel-and-easily-applicable-recurrence-predictor-in-localized-prostate-adenocarcinoma
#8
Pil-Jong Kim, Ji Y Park, Hong-Gee Kim, Yong Mee Cho, Heounjeong Go
OBJECTIVE: To identify new biomarkers for the biochemical recurrence (BCR) of prostate adenocarcinoma. PATIENTS AND METHODS: Clinical information of 500 prostate adenocarcinoma patients and their 152 RNA-sequencing and protein-array data from The Cancer Genome Atlas (TCGA) were separated into a discovery-set and a validation-set. Each dataset was analyzed according to the Gleason grade groups reflecting BCR. The results obtained from the analysis using TCGA dataset were confirmed by immunohistochemistry analyses of the confirmation cohort composed of 395 localized prostate adenocarcinoma patients...
January 20, 2017: BJU International
https://www.readbyqxmd.com/read/28077137/aberrant-methylation-of-dact1-and-dact2-are-associated-with-tumor-progression-and-poor-prognosis-in-esophageal-squamous-cell-carcinoma
#9
Yan-Li Guo, Bao-En Shan, Wei Guo, Zhi-Ming Dong, Zhen Zhou, Su-Peng Shen, Xin Guo, Jia Liang, Gang Kuang
BACKGROUND: The DACT (Dishevelled-associated antagonist of β-catenin) family of scaffold proteins may play important roles in tumorigenesis. However, the epigenetic changes of DACT1, 2, 3 and their effect on esophageal squamous cell carcinoma (ESCC) have not been investigated so far. The aim of this study was to investigate the promoter methylation and expression of DACT family, in order to elucidate more information on the role of DACT with regard to the progression and prognosis of ESCC...
January 11, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28041906/apc-c-fzr-cdh1-dependent-regulation-of-planar-cell-polarity-establishment-via-nek2-kinase-acting-on-dishevelled
#10
Ursula Weber, Marek Mlodzik
The Anaphase-Promoting Complex/Cyclosome (APC/C) is an E3 ubiquitin ligase, well known for its role in cell-cycle progression. However, it has been linked to additional functions, mainly in neuronal contexts, when using the co-activator Cdh1/Fzr. Here, our data indicate a post-mitotic requirement for the APC/C(Fzr/Cdh1) in epithelial cell patterning and planar cell polarity (PCP) in Drosophila. PCP signaling is critical for development by establishing cellular asymmetries and orientation within the plane of an epithelium, via differential localization of distinct complexes of core PCP factors...
January 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28035400/ampk-activators-suppress-breast-cancer-cell-growth-by-inhibiting-dvl3-facilitated-wnt-%C3%AE-catenin-signaling-pathway-activity
#11
Yu-Feng Zou, Chun-Wei Xie, Shi-Xin Yang, Jian-Ping Xiong
Adenosine monophosphate-activated protein kinase (AMPK) is a principal regulator of metabolism and the conservation of energy in cells, and protects them from exposure to various stressors. AMPK activators may exhibit therapeutic potential as suppressors of cell growth; however, the molecular mechanism underlying this phenomenon in various cancer cells remains to be fully elucidated. The present study investigated the effects of AMPK activators on breast cancer cell growth and specified the underlying molecular mechanism...
February 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28000796/identification-of-dep-domain-containing-proteins-by-a-machine-learning-method-and-experimental-analysis-of-their-expression-in-human-hcc-tissues
#12
Zhijun Liao, Xinrui Wang, Yeting Zeng, Quan Zou
The Dishevelled/EGL-10/Pleckstrin (DEP) domain-containing (DEPDC) proteins have seven members. However, whether this superfamily can be distinguished from other proteins based only on the amino acid sequences, remains unknown. Here, we describe a computational method to segregate DEPDCs and non-DEPDCs. First, we examined the Pfam numbers of the known DEPDCs and used the longest sequences for each Pfam to construct a phylogenetic tree. Subsequently, we extracted 188-dimensional (188D) and 20D features of DEPDCs and non-DEPDCs and classified them with random forest classifier...
December 21, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27939356/the-origins-of-rimmed-vacuoles-and-granulovacuolar-degeneration-bodies-are-associated-with-the-wnt-signaling-pathway
#13
Yukari Murata-Shinozaki, Tetsuya Takahashi, Tomoyasu Matsubara, Hirofumi Maruyama, Yuishin Izumi, Masayasu Matsumoto
Inclusion-body myositis (IBM) and Alzheimer's disease (AD) are biochemically characterized by the presence of aggregated β-amyloid protein and tau protein. In addition, both diseases are pathologically characterized by vacuolar changes, including rimmed vacuoles (RVs) in IBM and granulovacuolar degeneration (GVD) in AD. Previously, we demonstrated that RVs and GVD bodies are associated with a set of common molecules, leading us to speculate that both RVs and GVD bodies originate from similar structures on the plasma membrane of muscle cells and neuronal cells, namely, the neuromuscular junction (NMJ) and the postsynaptic spine especially in terms of Wnt signaling pathway...
December 7, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27932247/crystal-structure-of-the-pdz-domain-of-mouse-dishevelled-1-and-its-interaction-with-cxxc5
#14
Inhwan Lee, Sooho Choi, Ji-Hye Yun, Seolhwa Seo, Sehee Choi, Kang-Yell Choi, Weontae Lee
Dishevelled (Dvl) plays a crucial role in Wnt signaling by interacting with membrane-bound receptors and downstream molecules through its PDZ domain. CXXC5 is one of the key molecules that interacts with Dvl and negatively regulates the Wnt/β-catenin pathway in osteoblast differentiation. Recently, the Dvl-CXXC5 interaction has been identified as an excellent target for osteoporosis treatment. Therefore, it is desirable to have detailed structural information for the Dvl-CXXC5 interaction. Although solution structures of the Dvl1 PDZ domain have been reported, a high-resolution crystal structure would provide detailed sidechain information that is essential for drug development...
December 5, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27919787/modulation-of-post-translational-modifications-in-%C3%AE-catenin-and-lrp6-inhibits-wnt-signaling-pathway-in-pancreatic-cancer
#15
Bharti Garg, Bhuwan Giri, Kaustav Majumder, Vikas Dudeja, Sulagna Banerjee, Ashok Saluja
β-Catenin/Wnt signaling pathway is critically regulated in a normal cell by a number of post-translational modifications. In pancreatic cancer however, aberrant activation of this pathway plays a significant role in tumor progression and metastasis. Though a number of studies have focused on understanding Wnt signaling pathway in pancreatic cancer, there has been no systematic study to evaluate molecules that may be affecting this pathway. In the current study, we used a diterpene triepoxide, triptolide, to inhibit post-translational modifications in Wnt pathway and evaluated how this compound may be affecting the intricate signaling that regulates cell proliferation in pancreatic cancer...
March 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/27884142/dna-methylation-patterns-associated-with-oxidative-stress-in-an-ageing-population
#16
Åsa K Hedman, Mihkel Zilmer, Johan Sundström, Lars Lind, Erik Ingelsson
BACKGROUND: Oxidative stress has been related to type 2 diabetes (T2D) and cardiovascular disease (CVD), the leading global cause of death. Contributions of environmental factors such as oxidative stress on complex traits and disease may be partly mediated through changes in epigenetic marks (e.g. DNA methylation). Studies relating differential methylation with intermediate phenotypes and disease endpoints may be useful in identifying additional candidate genes and mechanisms involved in disease...
November 25, 2016: BMC Medical Genomics
https://www.readbyqxmd.com/read/27853583/the-core-planar-cell-polarity-gene-vangl2-directs-adult-corneal-epithelial-cell-alignment-and-migration
#17
Amy S Findlay, D Alessio Panzica, Petr Walczysko, Amy B Holt, Deborah J Henderson, John D West, Ann M Rajnicek, J Martin Collinson
This study shows that the core planar cell polarity (PCP) genes direct the aligned cell migration in the adult corneal epithelium, a stratified squamous epithelium on the outer surface of the vertebrate eye. Expression of multiple core PCP genes was demonstrated in the adult corneal epithelium. PCP components were manipulated genetically and pharmacologically in human and mouse corneal epithelial cells in vivo and in vitro. Knockdown of VANGL2 reduced the directional component of migration of human corneal epithelial (HCE) cells without affecting speed...
October 2016: Royal Society Open Science
https://www.readbyqxmd.com/read/27799526/prodigiosin-inhibits-wnt-%C3%AE-catenin-signaling-and-exerts-anticancer-activity-in-breast-cancer-cells
#18
Zhongyuan Wang, Bo Li, Liang Zhou, Shubin Yu, Zijie Su, Jiaxing Song, Qi Sun, Ou Sha, Xiaomei Wang, Wenqi Jiang, Karl Willert, Lei Wei, Dennis A Carson, Desheng Lu
Prodigiosin, a natural red pigment produced by numerous bacterial species, has exhibited promising anticancer activity; however, the molecular mechanisms of action of prodigiosin on malignant cells remain unclear. Aberrant activation of the Wnt/β-catenin signaling cascade is associated with numerous human cancers. In this study, we identified prodigiosin as a potent inhibitor of the Wnt/β-catenin pathway. Prodigiosin blocked Wnt/β-catenin signaling by targeting multiple sites of this pathway, including the low-density lipoprotein-receptor-related protein (LRP) 6, Dishevelled (DVL), and glycogen synthase kinase-3β (GSK3β)...
November 15, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27779255/lmo2-attenuates-tumor-growth-by-targeting-the-wnt-signaling-pathway-in-breast-and-colorectal-cancer
#19
Ye Liu, Di Huang, Zhaoyang Wang, Chao Wu, Zhao Zhang, Dan Wang, Zongjin Li, Tianhui Zhu, Shuang Yang, Wei Sun
The proto-oncogene LIM-domain only 2 (lmo2) was traditionally considered to be a pivotal transcriptional regulator in hematopoiesis and leukemia. Recently, the cytosolic localization of LMO2 was revealed in multiple epithelial tissues and a variety of solid tumors. However, the function of LMO2 in these epithelia and solid tumors remains largely unclear. The Wnt signaling pathway is a crucial determinant of development, and abnormalities in several key segments of this pathway contribute to oncogenesis. The current study demonstrated that LMO2 participates in the regulation of canonical Wnt signaling in the cytoplasm by binding to Dishevelled-1/2 (DVL-1/2) proteins...
October 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27758766/fzd7-frizzled-7-expressed-by-endothelial-cells-controls-blood-vessel-formation-through-wnt-%C3%AE-catenin-canonical-signaling
#20
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
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