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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
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 antagonism of Wnt signaling 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 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)...
March 16, 2018: Development
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
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
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
Josué Curto, Beatriz Del Valle-Pérez, Aida Villarroel, Guillem Fuertes, Meritxell Vinyoles, Raúl Peña, Antonio García de Herreros, Mireia Duñach
Canonical and non-canonical 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 non-canonical 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 non-canonical 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...
February 21, 2018: Molecular Oncology
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
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
Li Guo, Xiaohong Wang, Yuguang Yang, Hongchun Xu, Zhihong Zhang, Lili Yin, Yan Wang, Maopeng Yang, Shu Zhao, Shuping Bai, Ling Zhao, Zhipeng Wang, Xin Lian, Ying Liu, Qingyuan Zhang
The activation of the Wnt/β-catenin signaling pathway has been demonstrated to play important roles in breast carcinogenesis and to be associated with a poorer prognosis in breast cancer patients. However, genetic mutation is not the major reason for Wnt/β-catenin activation in breast cancer. Dishevelled-associated antagonist of β-catenin homolog 2 (DACT2) is a negative regulator of β-catenin and acts as a tumor suppressor in numerous cancer types; however, the expression change and potential role of DACT2 in breast cancer is unknown...
March 2018: Oncology Letters
Jianlei Xie, Meng Han, Miaojun Zhang, Haiteng Deng, Wei Wu
Dishevelled (Dvl) family proteins are key mediators of Wnt signalling and function in both canonical and noncanonical branches. Dvl2, the most studied Dvl protein, is extensively regulated by phosphorylation. Several kinases were found to be critical for Dvl2 localisation, stability control and functional segregation. For example, S143-phosphorylated Dvl2 was detected, together with CK1δ/ε, at the centrosome and basal body of primary cilia and plays pivotal roles during ciliogenesis. However, relatively less is known about Dvl dephosphorylation and the phosphatases involved...
February 9, 2018: Scientific Reports
Gaku Moriyama, Maya Tanigawa, Kosuke Sakai, Yusuke Hirata, Satoshi Kikuchi, Yuriko Saito, Hiroyuki Kyoyama, Kuniko Matsuda, Masahiro Seike, Akihiko Gemma, Kazutsugu Uematsu
It was previously revealed that Wnt signaling is activated in mesothelioma cells. Although epidermal growth factor receptor (EGFR) is expressed in mesothelioma cells, EGFR-tyrosine kinase inhibitors (TKIs) are not effective for mesothelioma treatment. However, in non-small cell lung cancer, the blocking of Wnt signaling has been identified to enhance the anticancer effect of EGFR-TKIs. To confirm the anticancer effect of blocking Wnt signaling in combination with EGFR-TKI treatment in mesothelioma, the present study evaluated the effect of simultaneous suppression of human dishevelled-3 (Dvl-3) expression with Dvl-3 small interfering RNA (siRNA) and of EGFR inhibition with gefitinib on mesothelioma cell viability...
January 2018: Oncology Letters
Janette Bester, Christina Matshailwe, Etheresia Pretorius
Circulating cytokines, and particularly the interleukin (IL)-family are known to play an important role in inflammation. These molecules circulate in the blood and therefore have a direct effect on the plasma molecules and the formed elements like the erythrocytes and platelets. Aberrant coagulation (hypercoagulation or blood clots that form too easily) and clot lyses (hypofibrinolysis, where clots do not dissolve properly, with an abnormally low rate of clot lysis time), are usually the hallmarks of many inflammatory conditions...
January 27, 2018: Cytokine
Kun Zhang, Minhui Li, Houyi Huang, Linpeng Li, Jie Yang, Li Feng, Junjie Gou, Mengju Jiang, Liaotian Peng, Linyi Chen, Ting Li, Ping Yang, Yuhan Yang, Yuanyuan Wang, Quekun Peng, Xiaozhen Dai, Tao Zhang
Multidrug resistance is a great obstacle in successful chemotherapy of colorectal cancer. However, the molecular mechanism underlying multidrug resistance is not fully understood. Dishevelled, a pivot in Wnt signaling, has been linked to cancer progression, while its role in chemoresistance remains unclear. Here, we found that Dishevelled1-3 was over-expressed in multidrug-resistant colorectal cancer cells (HCT-8/VCR) compared to their parental cells. Silencing Dishevelled1-3 resensitized HCT-8/VCR cells to multiple drugs including vincristine, 5-fluorouracil and oxaliplatin...
December 29, 2017: Oncotarget
Xin Sheng, Yuehua Liu, Junhua Wang, Xiaoqiong Li, Bo Shu
Objective To investigate the influence of different fluid shear stress (FSS) on Wnt/β signaling pathway in human umbilical vein endothelial cells (HUVECs) and its relationship with atherosclerosis. Methods HUVECs were subjected to different FSS (0, 1, 15 dynes/cm2) for various durations (6, 12, 18, 24 hours) using a shear stress device. Subsequently, real-time quantitative PCR was used to observe the mRNA expression levels of dishevelled 2 (Dvl2) and β-catenin in the Wnt signaling pathway, and immunofluorescence technology to observe their protein expression and localization...
December 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Wo-Tu Tian, Xiao-Jun Huang, Xiao Mao, Qing Liu, Xiao-Li Liu, Sheng Zeng, Xia-Nan Guo, Jun-Yi Shen, Yang-Qi Xu, Hui-Dong Tang, Xiao-Meng Yin, Mei Zhang, Wei-Guo Tang, Xiao-Rong Liu, Bei-Sha Tang, Sheng-Di Chen, Li Cao
BACKGROUND: Paroxysmal kinesigenic dyskinesia is the most common type of paroxysmal dyskinesia. Approximately half of the cases of paroxysmal kinesigenic dyskinesia worldwide are attributable to proline-rich transmembrane protein 2 mutations. OBJECTIVE: The objective of this study was to investigate potential causative genes and clinical characteristics in proline-rich transmembrane protein 2-negative patients with paroxysmal kinesigenic dyskinesia. METHODS: We analyzed clinical manifestations and performed exome sequencing in a cohort of 163 proline-rich transmembrane protein 2-negative probands, followed by filtering data with a paroxysmal movement disorders gene panel...
January 22, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
Jennifer K Heppert, Ariel M Pani, Allyson M Roberts, Daniel J Dickinson, Bob Goldstein
Oriented cell divisions are critical to establish and maintain cell fates and tissue organization. Diverse extracellular and intracellular cues have been shown to provide spatial information for mitotic spindle positioning, however, the molecular mechanisms by which extracellular signals communicate with cells to direct mitotic spindle positioning are largely unknown. In animal cells, oriented cell divisions are often achieved by the localization of force-generating, motor protein complexes to discrete cortical domains...
January 18, 2018: Genetics
Huaping Xiong, Ting Yan, Weijie Zhang, Fangfang Shi, Xuesong Jiang, Xiaohua Wang, Shoushan Li, Ying Chen, Cheng Chen, Yichao Zhu
Dishevelled-associated activator of morphogenesis 1 (Daam1) is a formin protein and participates in regulating cell migration of triple-negative breast cancer (TNBC) cells. The specific miRNA targeting Daam1 and mediating cell migration and invasion remains obscure. This experiment investigated the suppressive role of miR-613 in TNBC cells. The luciferase activity of Daam1 3'-untranslated region (3'-UTR) based reporters constructed in HEK-293T and MCF-7 cells suggested that Daam1 was the target gene of miR-613...
January 12, 2018: Cellular Signalling
Fei Xing, Wen-Juan Yi, Fang Miao, Meng-Yun Su, Tie-Chi Lei
Baicalin is a traditional Chinese herbal medicine commonly used for hair loss, the precise molecular mechanism of which is unknown. In the present study, the mechanism of baicalin was investigated via the topical application of baicalin to reconstituted hair follicles on mice dorsa and evaluating the effect on canonical Wnt/β‑catenin signaling in the hair follicles and the activity of dermal papillar cells. The results indicate that baicalin stimulates the expression of Wnt3a, Wnt5a, frizzled 7 and disheveled 2 whilst inhibiting the Axin/casein kinase 1α/adenomatous polyposis coli/glycogen synthase kinase 3β degradation complex, leading to accumulation of β‑catenin and activation of Wnt/β‑catenin signaling...
January 16, 2018: International Journal of Molecular Medicine
Vitezslav Kriz, Vladimir Korinek
In this review, we address aspects of Wnt, R-Spondin (RSPO) and Hippo signalling, in both healthy and transformed intestinal epithelium. In intestinal stem cells (ISCs), the Wnt pathway is essential for intestinal crypt formation and renewal, whereas RSPO-mediated signalling mainly affects ISC numbers. In human colorectal cancer (CRC), aberrant Wnt signalling is the driving mechanism initiating this type of neoplasia. The signalling role of the RSPO-binding transmembrane proteins, the leucine-rich-repeat-containing G-protein-coupled receptors (LGRs), is possibly more pleiotropic and not only limited to the enhancement of Wnt signalling...
January 8, 2018: Genes
Kimberly Siletti, Basile Tarchini, A J Hudspeth
The establishment of planar polarization by mammalian cells necessitates the integration of diverse signaling pathways. In the inner ear, at least two systems regulate the planar polarity of sensory hair bundles. The core planar cell polarity (PCP) proteins coordinate the orientations of hair cells across the epithelial plane. The cell-intrinsic patterning of hair bundles is implemented independently by the G protein complex classically known for orienting the mitotic spindle. Although the primary cilium also participates in each of these pathways, its role and the integration of the two systems are poorly understood...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
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