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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
#1
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
#2
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
#3
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...
December 29, 2016: 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
#4
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
#5
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
#6
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
#7
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...
December 3, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27884142/dna-methylation-patterns-associated-with-oxidative-stress-in-an-ageing-population
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27744318/essential-role-of-the-dishevelled-dep-domain-in-a-wnt-dependent-human-cell-based-complementation-assay
#13
Melissa V Gammons, Trevor J Rutherford, Zachary Steinhart, Stephane Angers, Mariann Bienz
Dishevelled (DVL) assembles Wnt signalosomes through dynamic head-to-tail polymerisation by means of its DIX domain. It thus transduces Wnt signals to cytoplasmic effectors including β-catenin, to control cell fates during normal development, tissue homeostasis and also in cancer. To date, most functional studies of Dishevelled relied on its Wnt-independent signalling activity resulting from overexpression, which is sufficient to trigger polymerisation, bypassing the requirement for Wnt signals. Here, we generate a human cell line devoid of endogenous Dishevelled (DVL1- DVL3), which lacks Wnt signal transduction to β-catenin...
October 15, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27729806/association-analysis-of-dact1-genetic-variants-and-gastric-cancer-risk-in-a-chinese-han-population-a-case-control-study
#14
Chi Huang, Younan Wang, Hao Fan, Xiang Ma, Ran Tang, Xiangkun Huan, Yi Zhu, Zekuan Xu, Hao Xu, Li Yang
PURPOSE: Disheveled-binding antagonist of beta-catenin 1 (DACT1) is involved in tumorigenesis through influencing cell apoptosis and proliferation. We aimed to investigate the effect of three tag single-nucleotide polymorphisms (SNPs) in DACT1 (rs863091 C>T, rs17832998 C>T, and rs167481 C>T) on the occurrence of gastric cancer (GC), their association with specific clinical characteristics, and consideration of the functional relevance of GC-related SNPs. SUBJECTS AND METHODS: In this hospital-based case-control study, the genotypes were acquired using the TaqMan-MGB method consisting of 602 cases and 602 controls...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27714812/dact1-a-wnt-pathway-inhibitor-mediates-human-mesangial-cell-tgf-%C3%AE-1-induced-apoptosis
#15
Daniele Pereira Jardim, Paula Cristina Eiras Poço, Alexandre Holthausen Campos
Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of men and women of all ages and racial groups. Loss of mesangial cells (MC) represents an early common feature in the pathogenesis of CKD. Transforming growth factor-β1 (TGF-β1) is a key inducer of kidney damage and triggers several pathological changes in renal cells, notably MC apoptosis. However, the mechanism of MC apoptosis induced by TGF-β1 remains elusive. Here we demonstrate for the first time a novel regulatory pathway in which the disheveled-binding antagonist of beta-catenin 1 (Dact1) gene is upregulated by TGF-β1, inducing MC apoptosis...
October 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27714636/mark2-par1b-insufficiency-attenuates-dvl-gene-transcription-via-histone-deacetylation-in-lumbosacral-spina-bifida
#16
Shuyuan Chen, Qin Zhang, Baoling Bai, Shengrong Ouyang, Yihua Bao, Huili Li, Ting Zhang
Dishevelled (DVL/Dvl) genes play roles in canonical and noncanonical Wnt signaling, both of which are essential in neural tube closing and are involved in balancing neural progenitor growth and differentiation, or neuroepithelial cell polarity, respectively. In mouse Dvl haploinsufficiency leads to neural tube defects (NTDs), which represent the second most common birth defects. However, DVL genes' genetic contributions in human NTDs are modest. We sought to explore the molecular impact on such genes in human NTDs in a Han Chinese cohort...
October 6, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27692984/wnt-signalosome-assembly-by-dep-domain-swapping-of-dishevelled
#17
Melissa V Gammons, Miha Renko, Christopher M Johnson, Trevor J Rutherford, Mariann Bienz
Extracellular signals are often transduced by dynamic signaling complexes ("signalosomes") assembled by oligomerizing hub proteins following their recruitment to signal-activated transmembrane receptors. A paradigm is the Wnt signalosome, which is assembled by Dishevelled via reversible head-to-tail polymerization by its DIX domain. Its activity causes stabilization of β-catenin, a Wnt effector with pivotal roles in animal development and cancer. How Wnt triggers signalosome assembly is unknown. Here, we use structural analysis, as well as biophysical and cell-based assays, to show that the DEP domain of Dishevelled undergoes a conformational switch, from monomeric to swapped dimer, to trigger DIX-dependent polymerization and signaling to β-catenin...
October 6, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27599467/the-expression-of-sfrp1-sfrp3-dvl1-and-dvl2-proteins-in-testicular-germ-cell-tumors
#18
Dora Fabijanovic, Iris Zunic, Tamara Nikuseva Martic, Faruk Skenderi, Ljiljana Serman, Semir Vranic
Germ cell tumors of the testis are a heterogeneous group of neoplasms that affect male adolescents and young adults. Wnt signaling pathway components have been shown to be actively involved in normal and malignant germ cell differentiation and progression. In this study, we aimed to explore the expression patterns of the secreted frizzled-related protein (SFRP) and Disheveled protein family (DVL) in a subset of testicular germ cell tumors. Eighty-five formalin-fixed, paraffin-embedded tissue samples of the primary germ cell tumors of the testis were stained against SFRP1, SFRP3, DVL1, and DVL2 proteins using immunohistochemistry...
November 2016: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/27536874/the-exon-junction-complex-regulates-the-splicing-of-cell-polarity-gene-dlg1-to-control-wingless-signaling-in-development
#19
Min Liu, Yajuan Li, Aiguo Liu, Ruifeng Li, Ying Su, Juan Du, Cheng Li, Alan Jian Zhu
Wingless (Wg)/Wnt signaling is conserved in all metazoan animals and plays critical roles in development. The Wg/Wnt morphogen reception is essential for signal activation, whose activity is mediated through the receptor complex and a scaffold protein Dishevelled (Dsh). We report here that the exon junction complex (EJC) activity is indispensable for Wg signaling by maintaining an appropriate level of Dsh protein for Wg ligand reception in Drosophila. Transcriptome analyses in Drosophila wing imaginal discs indicate that the EJC controls the splicing of the cell polarity gene discs large 1 (dlg1), whose coding protein directly interacts with Dsh...
2016: ELife
https://www.readbyqxmd.com/read/27530555/the-%C3%AE-protocadherin-c3-isoform-inhibits-canonical-wnt-signalling-by-binding-to-and-stabilizing-axin1-at-the-membrane
#20
Kar Men Mah, Douglas W Houston, Joshua A Weiner
The 22 γ-Protocadherin (γ-Pcdh) adhesion molecules encoded by the Pcdhg gene cluster play critical roles in nervous system development, including regulation of dendrite arborisation, neuronal survival, and synaptogenesis. Recently, they have been implicated in suppression of tumour cell growth by inhibition of canonical Wnt signalling, though the mechanisms through which this occurs remain unknown. Here, we show differential regulation of Wnt signalling by individual γ-Pcdhs: The C3 isoform uniquely inhibits the pathway, whilst 13 other isoforms upregulate signalling...
2016: Scientific Reports
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