DOCSLIB.ORG

Wnt Signaling Antibody Sampler

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Wnt Signaling Antibody Sampler Wnt Signaling Antibody Sampler Kit Store at -20°C 3 n 1 Kit Orders n 877-616-CELL (2355) (9 x 20 µl) [email protected] Support n 877-678-TECH (8324) [email protected] Web n www.cellsignal.com rev. 06/16 #2915 For Research Use Only. Not For Use In Diagnostic Procedures. Products Included Product # Quantity Mol. Wt. Isotype Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM Wnt3a (C64F2) Rabbit mAb 2721 20 µl 42 kDa Rabbit IgG NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C. Do not aliquot the antibodies. Wnt5a/b (C27E8) Rabbit mAb 2530 20 µl 45 kDa Rabbit IgG Recommended Antibody Dilutions: LRP6 (C47E12) Rabbit mAb 3395 20 µl 180, 210 kDa Rabbit IgG Western blotting 1:1000 Phospho-LRP6 (Ser1490) Antibody 2568 20 µl 180, 210 kDa Rabbit IgG Please visit www.cellsignal.com for validated data and a complete listing of recommended companion Dvl2 (30D2) Rabbit mAb 3224 20 µl 90–95 kDa Rabbit IgG products. Dvl3 Antibody 3218 20 µl 88–93 kDa Rabbit IgG U.S. Patent No. 5,675,063 Naked1 (C30F10) Rabbit mAb 2201 20 µl 59, 61 kDa Rabbit IgG Naked2 (C67C4) Rabbit mAb 2073 20 µl 59, 61 kDa Rabbit IgG Axin1 (C76H11) Rabbit mAb 2087 20 µl 110 kDa Rabbit IgG Anti-rabbit IgG, HRP-linked Antibody 7074 100 µl Goat See www.cellsignal.com for individual component applications, dilutions and additional application protocols. Description: The Wnt Signaling Antibody Sampler Kit Specificity/Sensitivity: Wnt3a (C64F2) Rabbit mAb Background References: provides an economical means of detecting integral proteins detects transfected Wnt3a protein in L cells and the (1) Cadigan, K.M. and Nusse, R. (1997) Genes Dev 11, within the Wnt signaling pathway. The kit includes enough conditioned medium from L/Wnt3a cells. Phospho-LRP6 3286–305. antibody to perform two western blot experiments with each (Ser1490) Antibody detects endogenous levels of LRP6 primary antibody. protein when phosphorylated at Ser1490. The remaining (2) Giles, R.H. et al. (2003) Biochim Biophys Acta 1653, 1–24. antibodies in the Wnt Signaling Sampler Kit detect endog- (3) Kohn, A.D. and Moon, R.T. Cell Calcium 38, 439–46. Background: The Wnt family includes several secreted enous levels of their respective total proteins. glycoproteins that play important roles in animal develop- (4) Logan, C.Y. and Nusse, R. (2004) Annu Rev Cell Dev Biol ment (1). Aberrant activation of Wnt signaling pathways Source/Purification: Monoclonal antibody is produced 20, 781–810. is involved in several types of cancers (2). Wnt members by immunizing animals with a synthetic peptide correspond- (5) Tamai, K. et al. (2000) Nature 407, 530–5. bind to the Frizzled family of proteins and activate several ing to residues surrounding Leu256 of human Wnt3a, signaling pathways (3). The canonical Wnt/β-catenin Glu176 of human Wnt5a, Met988 of human LRP6, Gly176 (6) Zeng, X. et al. (2005) Nature 438, 873–7. pathway requires a coreceptor from proteins belonging to of human Dvl2, Leu53 of human Naked1, and Ala217 of (7) Davidson, G. et al. (2005) Nature 438, 867–72. the low-density lipoprotein receptor (LDLR) family, such human Naked2. The monoclonal antibody for Axin1 is (8) Luo, W. and Lin, S.C. Neurosignals 13, 99–113. as LRP5 and LRP6 (4). Upon stimulation with Wnt, LRP6 produced by immunizing animals with recombinant human is phosphorylated by kinases such as GSK-3 and CK1 Axin1. The phospho-specific polyclonal antibody is pro- (9) Salahshor, S. and Woodgett, J.R. (2005) J Clin Pathol 58, and subsequently recruits Axin to the membrane (5-7). In duced by immunizing animals with a synthetic phospho- 225–36. the absence of Wnt stimulation, the multidomain scaffold peptide corresponding to residues surrounding Ser1490 of (10) Boutros, M. and Mlodzik, M. (1999) Mech Dev 83, 27–37. proteins Axin1 and Axin2 negatively regulate Wnt signaling. human LRP6. The total polyclonal antibody is produced by Axin1 complexes with APC, GSK-3β, Dvl and β-catenin immunizing animals with a synthetic peptide corresponding (11) Wharton, K.A. et al. (2001) Dev Biol 234, 93–106. and promotes the GSK-3β-mediated phosphorylation and to residues surrounding the carboxy terminus of human (12) Yan, D. et al. (2001) Proc Natl Acad Sci USA 98, 3802–7. subsequent degradation of β-catenin (8-9). The Disheveled Dvl3. Polyclonal antibodies are purified by Protein A and (Dsh) proteins (Dvl1, Dvl2 and Dvl3) inhibit glycogen syn- peptide affinity chromotagraphy. thase kinase-3β, thereby promoting β-catenin stabilization (4,10). Naked inhibits the canonical Wnt/β-catenin pathway by binding to Dsh proteins and directing Dsh activity towards the planar cell polarity pathway (11-12). is a trademark of Cell Signaling Technology, Inc. is a trademark of Cell Signaling Technology, ® Applications Key: W—Western IP—Immunoprecipitation IHC—Immunohistochemistry ChIP—Chromatin Immunoprecipitation IF—Immunofluorescence F—Flow cytometry E-P—ELISA-Peptide Species Cross-Reactivity Key: H—human M—mouse R—rat Hm—hamster Mk—monkey Mi—mink C—chicken Dm—D. melanogaster X—Xenopus Z—zebra fish B—bovine ® 2014 Cell Signaling Technology, Inc. ® 2014 Cell Signaling Technology, Cell Signaling Technology Dg—dog Pg—pig Sc—S. cerevisiae All—all species expected Species enclosed in parentheses are predicted to react based on 100% homology..
Load more

Recommended publications
  • The Crosstalk Between FAK and Wnt Signaling Pathways in Cancer and Its Therapeutic Implication
    International Journal of Molecular Sciences Review The Crosstalk between FAK and Wnt Signaling Pathways in Cancer and Its Therapeutic Implication Janine Wörthmüller * and Curzio Rüegg * Laboratory of Experimental and Translational Oncology, Pathology, Department of Oncology, Microbiology and Immunology (OMI), Faculty of Science and Medicine, University of Fribourg, CH-1700 Fribourg, Switzerland * Correspondence: [email protected] (J.W.); [email protected] (C.R.) Received: 31 October 2020; Accepted: 26 November 2020; Published: 30 November 2020 Abstract: Focal adhesion kinase (FAK) and Wnt signaling pathways are important contributors to tumorigenesis in several cancers. While most results come from studies investigating these pathways individually, there is increasing evidence of a functional crosstalk between both signaling pathways during development and tumor progression. A number of FAK–Wnt interactions are described, suggesting an intricate, context-specific, and cell type-dependent relationship. During development for instance, FAK acts mainly upstream of Wnt signaling; and although in intestinal homeostasis and mucosal regeneration Wnt seems to function upstream of FAK signaling, FAK activates the Wnt/β-catenin signaling pathway during APC-driven intestinal tumorigenesis. In breast, lung, and pancreatic cancers, FAK is reported to modulate the Wnt signaling pathway, while in prostate cancer, FAK is downstream of Wnt. In malignant mesothelioma, FAK and Wnt show an antagonistic relationship: Inhibiting FAK signaling activates the Wnt pathway and vice versa. As the identification of effective Wnt inhibitors to translate in the clinical setting remains an outstanding challenge, further understanding of the functional interaction between Wnt and FAK could reveal new therapeutic opportunities and approaches greatly needed in clinical oncology.
    [Show full text]
  • Wnt Signaling in Neuromuscular Junction Development
    Downloaded from http://cshperspectives.cshlp.org/ on September 23, 2021 - Published by Cold Spring Harbor Laboratory Press Wnt Signaling in Neuromuscular Junction Development Kate Koles and Vivian Budnik Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605 Correspondence: [email protected] Wnt proteins are best known for their profound roles in cell patterning, because they are required for the embryonic development of all animal species studied to date. Besides regulating cell fate, Wnt proteins are gaining increasing recognition for their roles in nervous system development and function. New studies indicate that multiple positive and negative Wnt signaling pathways take place simultaneously during the formation of verte- brate and invertebrate neuromuscular junctions. Although some Wnts are essential for the formation of NMJs, others appear to play a more modulatory role as part of multiple signaling pathways. Here we review the most recent findings regarding the function of Wnts at the NMJ from both vertebrate and invertebrate model systems. nt proteins are evolutionarily conserved, though important roles for Wnt signaling have Wsecreted lipo-glycoproteins involved in a become known from studies in both the central wide range of developmental processes in all and peripheral nervous system, this article is metazoan organisms examined to date. In ad- concerned with the role of Wnts at the NMJ. dition to governing many embryonic develop- mental processes, Wnt signaling is also involved WNT LIGANDS, RECEPTORS, AND WNT in nervous system maintenance and function, SIGNALING PATHWAYS and deregulation of Wnt signaling pathways oc- curs in many neurodegenerative and psychiatric Wnts and their receptors comprise a large fam- diseases (De Ferrari and Inestrosa 2000; Carica- ily of proteins.
    [Show full text]
  • Human B-Cell Proliferation and Intracellular Signaling: Part 3
    1872 Diabetes Volume 64, June 2015 Andrew F. Stewart,1 Mehboob A. Hussain,2 Adolfo García-Ocaña,1 Rupangi C. Vasavada,1 Anil Bhushan,3 Ernesto Bernal-Mizrachi,4 and Rohit N. Kulkarni5 Human b-Cell Proliferation and Intracellular Signaling: Part 3 Diabetes 2015;64:1872–1885 | DOI: 10.2337/db14-1843 This is the third in a series of Perspectives on intracel- signaling pathways in rodent and human b-cells, with lular signaling pathways coupled to proliferation in pan- a specific focus on the links between b-cell proliferation creatic b-cells. We contrast the large knowledge base in and intracellular signaling pathways (1,2). We highlight rodent b-cells with the more limited human database. what is known in rodent b-cells and compare and contrast With the increasing incidence of type 1 diabetes and that to the current knowledge base in human b-cells. In- the recognition that type 2 diabetes is also due in part variably, the human b-cell section is very brief compared fi b to a de ciency of functioning -cells, there is great ur- with the rodent counterpart, reflecting the still primitive gency to identify therapeutic approaches to expand hu- state of our understanding of mitogenic signaling in hu- b man -cell numbers. Therapeutic approaches might man b-cells. To emphasize this difference, each figure is include stem cell differentiation, transdifferentiation, or divided into two panels, one summarizing rodent b-cell expansion of cadaver islets or residual endogenous signaling and one for human b-cells. Our intended audi- b-cells. In these Perspectives, we focus on b-cell ence includes trainees in b-cell regeneration as well as proliferation.
    [Show full text]
  • Mechanisms of Wnt Signaling in Development
    P1: APR/ary P2: ARS/dat QC: ARS/APM T1: ARS August 29, 1998 9:42 Annual Reviews AR066-03 Annu. Rev. Cell Dev. Biol. 1998. 14:59–88 Copyright c 1998 by Annual Reviews. All rights reserved MECHANISMS OF WNT SIGNALING IN DEVELOPMENT Andreas Wodarz Institut f¨ur Genetik, Universit¨at D¨usseldorf, Universit¨atsstrasse 1, 40225 D¨usseldorf, Germany; e-mail: [email protected] Roel Nusse Howard Hughes Medical Institute and Department of Developmental Biology, Stanford University, Stanford, CA 94305-5428; e-mail: [email protected] KEY WORDS: Wnt, wingless, frizzled, catenin, signal transduction ABSTRACT Wnt genes encode a large family of secreted, cysteine-rich proteins that play key roles as intercellular signaling molecules in development. Genetic studies in Drosophila and Caenorhabditis elegans, ectopic gene expression in Xenopus, and gene knockouts in the mouse have demonstrated the involvement of Wnts in pro- cesses as diverse as segmentation, CNS patterning, and control of asymmetric cell divisions. The transduction of Wnt signals between cells proceeds in a complex series of events including post-translational modification and secretion of Wnts, binding to transmembrane receptors, activation of cytoplasmic effectors, and, finally, transcriptional regulation of target genes. Over the past two years our understanding of Wnt signaling has been substantially improved by the identifi- cation of Frizzled proteins as cell surface receptors for Wnts and by the finding that -catenin, a component downstream of the receptor, can translocate to the nucleus and function as a transcriptional activator. Here we review recent data that have started to unravel the mechanisms of Wnt signaling.
    [Show full text]
  • Mir-449 Overexpression Inhibits Papillary Thyroid Carcinoma Cell Growth by Targeting RET Kinase-Β-Catenin Signaling Pathway
    INTERNATIONAL JOURNAL OF ONCOLOGY 49: 1629-1637, 2016 miR-449 overexpression inhibits papillary thyroid carcinoma cell growth by targeting RET kinase-β-catenin signaling pathway ZONGYU LI1*, XIN HUANG2*, JINKAI XU1, QINGHUA SU1, JUN ZHAO1 and JIANCANG MA1 1Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University; 2Department of General Surgery, The Xi'an Central Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China Received May 20, 2016; Accepted July 13, 2016 DOI: 10.3892/ijo.2016.3659 Abstract. Papillary thyroid carcinoma (PTC) is the most miR-449 overexpression inhibited the growth of PTC by inac- common thyroid cancer and represent approximately 80% of tivating the β-catenin pathway. Thus, miR-449 may serve as a all thyroid cancers. The present study is aimed to investigate potential therapeutic strategy for the treatment of PTC. the role of microRNA (miR)-449 in the progression of PTC. Our results revealed that miR-449 was underexpressed in Introduction the collected PTC specimens compared with non-cancerous PTC tissues. Overexpression of miR-449 induced a cell cycle Thyroid cancer is the leading cause of increased morbidity and arrest at G0/G1 phase and inhibited PTC cell growth in vitro. mortality for endocrine malignancies, and papillary thyroid Further studies revealed that RET proto-oncogene (RET) is carcinoma (PTC) accounts for 80% of thyroid cancer cases (1). a novel miR-449 target, due to miR-449 bound directly to Reports have indicated that PTC have a homogeneous molec- its 3'-untranslated region and miR-449 mimic reduced the ular signature during tumorigenesis compared with other protein expression of RET.
    [Show full text]
  • CIRP Promotes the Progression of Non-Small Cell Lung Cancer Through
    Liao et al. Journal of Experimental & Clinical Cancer Research (2021) 40:275 https://doi.org/10.1186/s13046-021-02080-9 RESEARCH Open Access CIRP promotes the progression of non- small cell lung cancer through activation of Wnt/β-catenin signaling via CTNNB1 Yi Liao1,2†, Jianguo Feng3†, Weichao Sun1, Chao Wu2, Jingyao Li1, Tao Jing4, Yuteng Liang5, Yonghui Qian5, Wenlan Liu1,5* and Haidong Wang2* Abstract Background: Cold-inducible RNA binding protein (CIRP) is a newly discovered proto-oncogene. In this study, we investigated the role of CIRP in the progression of non-small cell lung cancer (NSCLC) using patient tissue samples, cultured cell lines and animal lung cancer models. Methods: Tissue arrays, IHC and HE staining, immunoblotting, and qRT-PCR were used to detect the indicated gene expression; plasmid and siRNA transfections as well as viral infection were used to manipulate gene expression; cell proliferation assay, cell cycle analysis, cell migration and invasion analysis, soft agar colony formation assay, tail intravenous injection and subcutaneous inoculation of animal models were performed to study the role of CIRP in NSCLC cells; Gene expression microarray was used to select the underlying pathways; and RNA immunoprecipitation assay, biotin pull-down assay, immunopurification assay, mRNA decay analyses and luciferase reporter assay were performed to elucidate the mechanisms. The log-rank (Mantel-Cox) test, independent sample T- test, nonparametric Mann-Whitney test, Spearman rank test and two-tailed independent sample T-test were used accordingly in our study. Results: Our data showed that CIRP was highly expressed in NSCLC tissue, and its level was negatively correlated with the prognosis of NSCLC patients.
    [Show full text]
  • The Role of Signaling Pathways in the Development and Treatment of Hepatocellular Carcinoma
    Oncogene (2010) 29, 4989–5005 & 2010 Macmillan Publishers Limited All rights reserved 0950-9232/10 www.nature.com/onc REVIEW The role of signaling pathways in the development and treatment of hepatocellular carcinoma S Whittaker1,2, R Marais3 and AX Zhu4 1Dana-Farber Cancer Institute, Boston, MA, USA; 2The Broad Institute, Cambridge, MA, USA; 3Institute of Cancer Research, London, UK and 4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA Hepatocellular carcinoma (HCC) is a highly prevalent, malignancy in adults (Pons-Renedo and Llovet, 2003). treatment-resistant malignancy with a multifaceted mole- For the vast majority of patients, HCC is a late cular pathogenesis. Current evidence indicates that during complication of chronic liver disease, and as such, is hepatocarcinogenesis, two main pathogenic mechanisms often associated with cirrhosis. The main risk factors for prevail: (1) cirrhosis associated with hepatic regeneration the development of HCC include infection with hepatitis after tissue damage caused by hepatitis infection, toxins B virus (HBV) or hepatitis C virus (HCV). Hepatitis (for example, alcohol or aflatoxin) or metabolic influ- infection is believed to be the main etiologic factor in ences, and (2) mutations occurring in single or multiple 480% of cases (Anzola, 2004). Other risk factors oncogenes or tumor suppressor genes. Both mechanisms include excessive alcohol consumption, nonalcoholic have been linked with alterations in several important steatohepatitis, autoimmune hepatitis, primary biliary cellular signaling pathways. These pathways are of cirrhosis, exposure to environmental carcinogens (parti- interest from a therapeutic perspective, because targeting cularly aflatoxin B) and the presence of various genetic them may help to reverse, delay or prevent tumorigenesis.
    [Show full text]
  • Beta;-Catenin Signaling in Rhabdomyosarcoma
    Laboratory Investigation (2013) 93, 1090–1099 & 2013 USCAP, Inc All rights reserved 0023-6837/13 Characterization of Wnt/b-catenin signaling in rhabdomyosarcoma Srinivas R Annavarapu1,8,9, Samantha Cialfi2,9, Carlo Dominici2,3, George K Kokai4, Stefania Uccini5, Simona Ceccarelli6, Heather P McDowell2,3,7 and Timothy R Helliwell1 Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and accounts for about 5% of all malignant paediatric tumours. b-Catenin, a multifunctional nuclear transcription factor in the canonical Wnt signaling pathway, is active in myogenesis and embryonal somite patterning. Dysregulation of Wnt signaling facilitates tumour invasion and metastasis. This study characterizes Wnt/b-catenin signaling and functional activity in paediatric embryonal and alveolar RMS. Immunohistochemical assessment of paraffin-embedded tissues from 44 RMS showed b-catenin expression in 26 cases with cytoplasmic/membranous expression in 9/14 cases of alveolar RMS, and 15/30 cases of embryonal RMS, whereas nuclear expression was only seen in 2 cases of embryonal RMS. The potential functional significance of b-catenin expression was tested in four RMS cell lines, two derived from embryonal (RD and RD18) RMS and two from alveolar (Rh4 and Rh30) RMS. Western blot analysis demonstrated the expression of Wnt-associated proteins including b-catenin, glycogen synthase kinase-3b, disheveled, axin-1, naked, LRP-6 and cadherins in all cell lines. Cell fractionation and immunofluorescence studies of the cell lines (after stimulation by human recombinant Wnt3a) showed reduced phosphorylation of b-catenin, stabilization of the active cytosolic form and nuclear translocation of b-catenin. Reporter gene assay demonstrated a T-cell factor/lymphoid-enhancing factor-mediated transactivation in these cells.
    [Show full text]
  • Loss of RET Promotes Mesenchymal Identity in Neuroblastoma Cells
    cancers Article Loss of RET Promotes Mesenchymal Identity in Neuroblastoma Cells Joachim T. Siaw 1,†, Jonatan L. Gabre 1,2,† , Ezgi Uçkun 1 , Marc Vigny 3, Wancun Zhang 4, Jimmy Van den Eynden 2 , Bengt Hallberg 1 , Ruth H. Palmer 1 and Jikui Guan 1,4,* 1 Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE-40530 Gothenburg, Sweden; [email protected] (J.T.S.); [email protected] (J.L.G.); [email protected] (E.U.); [email protected] (B.H.); [email protected] (R.H.P.) 2 Anatomy and Embryology Unit, Department of Human Structure and Repair, Ghent University, 9000 Ghent, Belgium; [email protected] 3 Université Pierre et Marie Curie, UPMC, INSERM UMRS-839, 75005 Paris, France; [email protected] 4 Department of Pediatric Oncology Surgery, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, China; [email protected] * Correspondence: [email protected] † These authors contributed equally to this work. Simple Summary: The anaplastic lymphoma kinase (ALK) and rearranged during transfection (RET) receptor tyrosine kinases (RTKs) are expressed in both the developing neural crest and the pediatric cancer neuroblastoma. Moreover, ALK is mutated in approximately 10% of neuroblastomas. Here, we investigated ALK and RET in neuroblastoma, with the aim of better understanding their respective contributions. Using neuroblastoma cell lines, we show that ALK modulates RET signaling at the level of RET phosphorylation, as well as at the level of transcription. Using CRISPR/Cas9, we generated Citation: Siaw, J.T.; Gabre, J.L.; Uçkun, E.; Vigny, M.; Zhang, W.; Van RET knockout neuroblastoma cell lines and performed a multi-omics approach, combining RNA-Seq den Eynden, J.; Hallberg, B.; Palmer, and proteomics to characterize the effect of deleting RET in a neuroblastoma context.
    [Show full text]
  • Wnt3a Upregulates Brain-Derived Insulin by Increasing Neurod1 Via
    Lee et al. Molecular Brain (2016) 9:24 DOI 10.1186/s13041-016-0207-5 RESEARCH Open Access Wnt3a upregulates brain-derived insulin by increasing NeuroD1 via Wnt/β-catenin signaling in the hypothalamus Jaemeun Lee1, Kyungchan Kim1, Seong-Woon Yu1 and Eun-Kyoung Kim1,2* Abstract Background: Insulin plays diverse roles in the brain. Although insulin produced by pancreatic β-cells that crosses the blood–brain barrier is a major source of brain insulin, recent studies suggest that insulin is also produced locally within the brain. However, the mechanisms underlying the production of brain-derived insulin (BDI) are not yet known. Results: Here, we examined the effect of Wnt3a on BDI production in a hypothalamic cell line and hypothalamic tissue. In N39 hypothalamic cells, Wnt3a treatment significantly increased the expression of the Ins2 gene, which encodes the insulin isoform predominant in the mouse brain, by activating Wnt/β-catenin signaling. The concentration of insulin was higher in culture medium of Wnt3a-treated cells than in that of untreated cells. Interestingly, neurogenic differentiation 1 (NeuroD1), a target of Wnt/β-catenin signaling and one of transcription factors for insulin, was also induced by Wnt3a treatment in a time- and dose-dependent manner. In addition, the treatment of BIO, a GSK3 inhibitor, also increased the expression of Ins2 and NeuroD1. Knockdown of NeuroD1 by lentiviral shRNAs reduced the basal expression of Ins2 and suppressed Wnt3a-induced Ins2 expression. To confirm the Wnt3a-induced increase in Ins2 expression in vivo, Wnt3a was injected into the hypothalamus of mice. Wnt3a increased the expression of NeuroD1 and Ins2 in the hypothalamus in a manner similar to that observed in vitro.
    [Show full text]
  • Potential Signaling Pathways As Therapeutic Targets for Overcoming Chemoresistance in Mucinous Ovarian Cancer (Review)
    BIOMEDICAL REPORTS 8: 215-223, 2018 Potential signaling pathways as therapeutic targets for overcoming chemoresistance in mucinous ovarian cancer (Review) EMIKO NIIRO, SACHIKO MORIOKA, KANA IWAI, YUKI YAMADA, KENJI OGAWA, NAOKI KAWAHARA and HIROSHI KOBAYASHI Department of Obstetrics and Gynecology, Nara Medical University, Kashihara, Nara 634-8522, Japan Received December 29, 2017; Accepted January 10, 2018 DOI: 10.3892/br.2018.1045 Abstract. Cases of mucinous ovarian cancer are predomi- Contents nantly resistant to chemotherapies. The present review summarizes current knowledge of the therapeutic potential 1. Introduction of targeting the Wingless (WNT) pathway, with particular 2. Potential candidate gene alterations in mucinous ovarian emphasis on preclinical and clinical studies, for improving the cancer chemoresistance and treatment of mucinous ovarian cancer. A 3. Growth factor and WNT pathways review was conducted of English language literature published 4. Molecular mechanism of WNT signaling implicated in between January 2000 and October 2017 that concerned chemoresistance potential signaling pathways associated with the chemoresis- 5. WNT-related potential candidates for overcoming chemo- tance of mucinous ovarian cancer. The literature indicated that resistance aberrant activation of growth factor and WNT signaling path- 6. Combination of cytotoxic agents with therapeutic antibodies ways is specifically observed in mucinous ovarian cancer. An or sensitizing agents evolutionarily conserved signaling cascade system including 7.
    [Show full text]
  • Ror2 Functions As a Noncanonical Wnt Receptor That Regulates NMDAR-Mediated Synaptic Transmission
    RoR2 functions as a noncanonical Wnt receptor that regulates NMDAR-mediated synaptic transmission Waldo Cerpaa,1, Elena Latorre-Estevesa,b, and Andres Barriaa,2 aDepartment of Physiology and Biophysics and bMolecular and Cellular Biology Program, University of Washington, Seattle, WA 98195 Edited* by Richard L. Huganir, The Johns Hopkins University School of Medicine, Baltimore, MD, and approved March 6, 2015 (received for review September 16, 2014) Wnt signaling has a well-established role as a regulator of nervous receptor for noncanonical Wnt ligands capable of regulating syn- system development, but its role in the maintenance and regula- aptic NMDARs. In hippocampal neurons, activation of RoR2 by tion of established synapses in the mature brain remains poorly noncanonical Wnt ligand Wnt5a activates PKC and JNK, two understood. At excitatory glutamatergic synapses, NMDA receptors kinases involved in the regulation of NMDAR currents. In ad- (NMDARs) have a fundamental role in synaptogenesis, synaptic dition, we show that signaling through RoR2 is necessary for plasticity, and learning and memory; however, it is not known what the maintenance of basal NMDAR-mediated synaptic trans- controls their number and subunit composition. Here we show that mission and the acute regulation of NMDAR synaptic responses the receptor tyrosine kinase-like orphan receptor 2 (RoR2) func- by Wnt5a. tions as a Wnt receptor required to maintain basal NMDAR- Identification of RoR2 as a Wnt receptor that regulates syn- aptic NMDARs provides a mechanism for Wnt signaling to mediated synaptic transmission. In addition, RoR2 activation by a control synaptic transmission and synaptic plasticity acutely, and noncanonical Wnt ligand activates PKC and JNK and acutely en- is a critical first step toward understanding the role played by hances NMDAR synaptic responses.
    [Show full text]