Genomes and Genes
Summary: A proto-oncogene protein and member of the Wnt family of proteins. It is expressed in the caudal MIDBRAIN and is essential for proper development of the entire mid-/hindbrain region.
- Nogueira L, Dunlap S, Ford N, Hursting S. Calorie restriction and rapamycin inhibit MMTV-Wnt-1 mammary tumor growth in a mouse model of postmenopausal obesity. Endocr Relat Cancer. 2012;19:57-68 pubmed publisher..We conclude that mTOR inhibition may be a pharmacologic strategy to mimic the anticancer effects of CR and break the obesity-breast cancer progression link. ..
- Pérez Garijo A, Shlevkov E, Morata G. The role of Dpp and Wg in compensatory proliferation and in the formation of hyperplastic overgrowths caused by apoptotic cells in the Drosophila wing disc. Development. 2009;136:1169-77 pubmed publisher..In compartments containing undead cells, the adventitious Dpp/Wg signalling results in hyperplastic overgrowths. ..
- Smith Bolton R, Worley M, Kanda H, Hariharan I. Regenerative growth in Drosophila imaginal discs is regulated by Wingless and Myc. Dev Cell. 2009;16:797-809 pubmed publisher..This system is conducive to forward genetic screens, enabling an unbiased search for genes that regulate both the extent of and the capacity for regeneration. ..
- Mitchell N, Cranna N, Richardson H, Quinn L. The Ecdysone-inducible zinc-finger transcription factor Crol regulates Wg transcription and cell cycle progression in Drosophila. Development. 2008;135:2707-16 pubmed publisher..Taken together, our studies have revealed a novel mechanism for cell cycle regulation, whereby Crol links steroid hormone signals to Wg signalling and the regulation of crucial cell cycle targets. ..
- Korkut C, Ataman B, Ramachandran P, Ashley J, Barria R, Gherbesi N, et al. Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless. Cell. 2009;139:393-404 pubmed publisher..For a video summary of this article, see the PaperFlick file with the Supplemental Data available online. ..
- Lu Y, Bertran S, Samuels T, Mira y Lopez R, Farias E. Mechanism of inhibition of MMTV-neu and MMTV-wnt1 induced mammary oncogenesis by RARalpha agonist AM580. Oncogene. 2010;29:3665-76 pubmed publisher..The anticancer effect of RARalpha, together with the newly discovered pro-proliferative role of RARgamma, suggests that specific activation of RARalpha and inhibition of RARgamma might be effective in breast cancer therapy. ..
- Huang T, Liu Y, Huang M, Zhao X, Cheng L. Wnt1-cre-mediated conditional loss of Dicer results in malformation of the midbrain and cerebellum and failure of neural crest and dopaminergic differentiation in mice. J Mol Cell Biol. 2010;2:152-63 pubmed publisher..We then demonstrated that the development of dopaminergic neurons was impaired in Dicer-deleted mice. Our studies therefore suggest that miRNAs contribute to the embryonic development in multiple locations. ..
- Shang Y, Chong Z, Hou J, Maiese K. Wnt1, FoxO3a, and NF-kappaB oversee microglial integrity and activation during oxidant stress. Cell Signal. 2010;22:1317-29 pubmed publisher..Our work highlights Wnt1 and the control of novel downstream transcriptional pathways as critical components for the oversight of nervous system microglial cells. ..
- Nunez N, Perkins S, Smith N, Berrigan D, Berendes D, Varticovski L, et al. Obesity accelerates mouse mammary tumor growth in the absence of ovarian hormones. Nutr Cancer. 2008;60:534-41 pubmed publisher..In contrast, maintaining a lean body weight phenotype was associated with reduced Wnt-1 tumor growth regardless of ovarian hormone status. ..
- Pond A, Herschkowitz J, Schwertfeger K, Welm B, Zhang Y, York B, et al. Fibroblast growth factor receptor signaling dramatically accelerates tumorigenesis and enhances oncoprotein translation in the mouse mammary tumor virus-Wnt-1 mouse model of breast cancer. Cancer Res. 2010;70:4868-79 pubmed publisher..Further, they reveal protein translation initiation factors as potential therapeutic targets for human breast cancers with alterations in FGF signaling. ..
- Zecca M, Struhl G. A feed-forward circuit linking wingless, fat-dachsous signaling, and the warts-hippo pathway to Drosophila wing growth. PLoS Biol. 2010;8:e1000386 pubmed publisher..We posit that Wg propels wing growth at least in part by fueling a wave front of Ft-Ds signaling that propagates vg expression from one cell to the next. ..
- Lin G, Xu N, Xi R. Paracrine Wingless signalling controls self-renewal of Drosophila intestinal stem cells. Nature. 2008;455:1119-23 pubmed publisher..The identification of the Drosophila ISC niche and the principal self-renewal signal will facilitate further understanding of intestinal homeostasis control and tumorigenesis. ..
- Ettenberg S, Charlat O, Daley M, Liu S, Vincent K, Stuart D, et al. Inhibition of tumorigenesis driven by different Wnt proteins requires blockade of distinct ligand-binding regions by LRP6 antibodies. Proc Natl Acad Sci U S A. 2010;107:15473-8 pubmed publisher..Our studies provide insights into Wnt-induced LRP5/6 activation and show the potential utility of LRP6 antibodies in Wnt-driven cancer. ..
- Sanchez L, Chaouiya C, Thieffry D. Segmenting the fly embryo: logical analysis of the role of the segment polarity cross-regulatory module. Int J Dev Biol. 2008;52:1059-75 pubmed publisher..Finally, the simulation of altered expressions of segment polarity genes leads to results consistent with the published data. ..
- Lee H, Uen Y, Tian Y, Sun C, Sheu M, Kuo H, et al. Wnt-1 protein as a prognostic biomarker for hepatitis B-related and hepatitis C-related hepatocellular carcinoma after surgery. Cancer Epidemiol Biomarkers Prev. 2009;18:1562-9 pubmed publisher..The use of tumor Wnt-1 as prognostic biomarker may identify patients with HBV- and/or HCV-related HCC patients with a high risk of tumor recurrence who may then benefit from further intensive therapy after surgery. ..
- Schubiger M, Sustar A, Schubiger G. Regeneration and transdetermination: the role of wingless and its regulation. Dev Biol. 2010;347:315-24 pubmed publisher..We speculate that this lessens repression of dpp dorsally, and thus creates a permissive condition under which the balance of ectopic Wg and Dpp is favorable for transdetermination. ..
- Pepperl J, Reim G, Lüthi U, Kaech A, Hausmann G, Basler K. Sphingolipid depletion impairs endocytic traffic and inhibits Wingless signaling. Mech Dev. 2013;130:493-505 pubmed publisher..Our results underscore this and support the view that sphingolipid levels are crucial in orchestrating epithelial endocytic trafficking in vivo. They further demonstrate that ceramide/sphingolipid levels can affect Wnt signaling. ..
- Kim Y, Clark R, Ranheim E, Alexander C. Wnt1 expression induces short-range and long-range cell recruitments that modify mammary tumor development and are not induced by a cell-autonomous beta-catenin effector. Cancer Res. 2008;68:10145-53 pubmed publisher..Thus, localized ectopic expression of the proto-oncogene Wnt1 in mammary glands induces systemic responses, and we propose that this response modifies the tumorigenic outcome. ..
- Choe C, Brown S. Genetic regulation of engrailed and wingless in Tribolium segmentation and the evolution of pair-rule segmentation. Dev Biol. 2009;325:482-91 pubmed publisher..Conserved interactions between eve and prd at the anterior boundary of odd-numbered parasegments may reflect an ancestral segmentation mechanism that functioned in every segment prior to the evolution of pair-rule segmentation...
- Wang Z, Xu L, Zhu X, Cui W, Sun Y, Nishijo H, et al. Demethylation of specific Wnt/?-catenin pathway genes and its upregulation in rat brain induced by prenatal valproate exposure. Anat Rec (Hoboken). 2010;293:1947-53 pubmed publisher..This work suggested an epigenetic action via which VPA, when administered in early pregnancy, induced dysregulation of signaling pathway, further facilitating susceptibility to ASDs. ..
- Vaillant F, Asselin Labat M, Shackleton M, Forrest N, Lindeman G, Visvader J. The mammary progenitor marker CD61/beta3 integrin identifies cancer stem cells in mouse models of mammary tumorigenesis. Cancer Res. 2008;68:7711-7 pubmed publisher..Overall, our findings show the utility of the progenitor marker CD61 in the identification of CSCs that sustain specific mammary tumors...
- Nagaraj R, Banerjee U. Regulation of Notch and Wingless signalling by phyllopod, a transcriptional target of the EGFR pathway. EMBO J. 2009;28:337-46 pubmed publisher..Furthermore, this study identifies a Phyl-regulated class of endosomal vesicles that specifically include components of Notch and Wg signalling. ..
- Casali A, Batlle E. Intestinal stem cells in mammals and Drosophila. Cell Stem Cell. 2009;4:124-7 pubmed publisher..Here we review recent developments in this exciting field, paying special attention to the characterization of Drosophila and mammalian intestinal stem cells. ..
- Chong Z, Shang Y, Hou J, Maiese K. Wnt1 neuroprotection translates into improved neurological function during oxidant stress and cerebral ischemia through AKT1 and mitochondrial apoptotic pathways. Oxid Med Cell Longev. 2010;3:153-65 pubmed publisher..Our work identifies Wnt1 and its downstream signaling as cellular targets with high clinical potential for novel treatment strategies for multiple disorders precipitated by oxidative stress. ..
- Dai C, Stolz D, Kiss L, Monga S, Holzman L, Liu Y. Wnt/beta-catenin signaling promotes podocyte dysfunction and albuminuria. J Am Soc Nephrol. 2009;20:1997-2008 pubmed publisher..These results suggest that targeting hyperactive Wnt/beta-catenin signaling may represent a novel therapeutic strategy for proteinuric kidney diseases. ..
- Lin G, Xi R. Intestinal stem cell, muscular niche and Wingless signaling. Fly (Austin). 2008;2:310-2 pubmed..Here we provide a brief overview of our findings, and discuss future perspectives on the regulatory mechanisms underlying ISC self-renewal and differentiation. ..
- Shang Y, Chong Z, Wang S, Maiese K. Erythropoietin and Wnt1 govern pathways of mTOR, Apaf-1, and XIAP in inflammatory microglia. Curr Neurovasc Res. 2011;8:270-85 pubmed..These studies offer new insights for the development of innovative therapeutic strategies for neurodegenerative disorders that focus upon inflammatory microglia and novel signal transduction pathways. ..
- Cordero J, Cagan R. Canonical wingless signaling regulates cone cell specification in the Drosophila retina. Dev Dyn. 2010;239:875-84 pubmed publisher..This activity requires canonical Wg signaling and is linked with Notch pathway activity. Our work broadens the role of canonical Wg signaling to encompass multiple patterning steps in the emerging Drosophila retina. ..
- Baker R, Kent C, Silbermann R, Hassell J, Young L, Howe L. Pea3 transcription factors and wnt1-induced mouse mammary neoplasia. PLoS ONE. 2010;5:e8854 pubmed publisher..Furthermore, this study provides evidence for a protumorigenic role of PEA3 factors in breast neoplasia, and supports targeting the PEA3 transcription factor family in breast cancer. ..
- Lindeman G, Visvader J. Insights into the cell of origin in breast cancer and breast cancer stem cells. Asia Pac J Clin Oncol. 2010;6:89-97 pubmed publisher..Although many unresolved questions on CSCs remain, ongoing efforts to identify and characterize CSCs continue to be an important area of investigation, with the potential to identify novel tumor targeting strategies. ..
- Ohsawa S, Sato Y, Enomoto M, Nakamura M, Betsumiya A, Igaki T. Mitochondrial defect drives non-autonomous tumour progression through Hippo signalling in Drosophila. Nature. 2012;490:547-51 pubmed publisher..Our findings provide a mechanistic basis for interclonal tumour progression driven by mitochondrial dysfunction and oncogenic Ras...
- Huang C, Liu D, Ishikawa S, Nakashima T, Nakashima N, Yokomise H, et al. Wnt1 overexpression promotes tumour progression in non-small cell lung cancer. Eur J Cancer. 2008;44:2680-8 pubmed publisher..0127). The Wnt1 overexpression is associated with the expression of tumour-associated Wnt-targets, tumour proliferation, angiogenesis and a poor prognosis in NSCLCs. ..
- Teissedre B, PINDERHUGHES A, Incassati A, Hatsell S, Hiremath M, Cowin P. MMTV-Wnt1 and -DeltaN89beta-catenin induce canonical signaling in distinct progenitors and differentially activate Hedgehog signaling within mammary tumors. PLoS ONE. 2009;4:e4537 pubmed publisher..They further suggest that Hedgehog pathway activation maybe a critical component and useful indicator of breast tumors arising from unopposed Wnt1 ligand...
- Chen J, Luo Q, Yuan Y, Huang X, Cai W, Li C, et al. Pygo2 associates with MLL2 histone methyltransferase and GCN5 histone acetyltransferase complexes to augment Wnt target gene expression and breast cancer stem-like cell expansion. Mol Cell Biol. 2010;30:5621-35 pubmed publisher..This work now links mechanistically Pygo2's role in histone modification to its enhancement of the Wnt-dependent transcriptional program and cancer stem-like cell expansion. ..
- Wexler E, Rosen E, Lu D, Osborn G, Martin E, Raybould H, et al. Genome-wide analysis of a Wnt1-regulated transcriptional network implicates neurodegenerative pathways. Sci Signal. 2011;4:ra65 pubmed publisher..These unbiased and genome-wide analyses provide evidence for a connection between Wnt signaling and the transcriptional regulation of neurodegenerative disease genes. ..
- Doubravska L, Krausova M, Gradl D, Vojtechova M, Tumova L, Lukas J, et al. Fatty acid modification of Wnt1 and Wnt3a at serine is prerequisite for lipidation at cysteine and is essential for Wnt signalling. Cell Signal. 2011;23:837-48 pubmed publisher..Finally, we show that the signalling competency of both Wnt1 and Wnt3a is related to their ability to associate with the extracellular matrix. ..
- Xu N, Wang S, Tan D, Gao Y, Lin G, Xi R. EGFR, Wingless and JAK/STAT signaling cooperatively maintain Drosophila intestinal stem cells. Dev Biol. 2011;354:31-43 pubmed publisher..Taken together, our data suggest that Drosophila midgut ISCs are maintained cooperatively by multiple signaling pathway activities and reinforce the notion that visceral muscle is a critical component of the ISC niche. ..
- Barrott J, Cash G, Smith A, Barrow J, Murtaugh L. Deletion of mouse Porcn blocks Wnt ligand secretion and reveals an ectodermal etiology of human focal dermal hypoplasia/Goltz syndrome. Proc Natl Acad Sci U S A. 2011;108:12752-7 pubmed publisher..Conditional deletion of Porcn thus provides an experimental model of FDH, as well as a valuable tool to probe Wnt ligand function in vivo...
- Corada M, Nyqvist D, Orsenigo F, Caprini A, Giampietro C, Taketo M, et al. The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signaling. Dev Cell. 2010;18:938-49 pubmed publisher..We propose that early and sustained beta-catenin signaling prevents correct endothelial cell differentiation, altering vascular remodeling and arteriovenous specification. ..
- Wittmann D, Blöchl F, Trumbach D, Wurst W, Prakash N, Theis F. Spatial analysis of expression patterns predicts genetic interactions at the mid-hindbrain boundary. PLoS Comput Biol. 2009;5:e1000569 pubmed publisher..We show, in particular, that the spatial gene expression patterns around the MHB help us to understand the maintenance of this boundary on a systems level. ..
- Fu J, Ivy Yu H, Maruyama T, Mirando A, Hsu W. Gpr177/mouse Wntless is essential for Wnt-mediated craniofacial and brain development. Dev Dyn. 2011;240:365-71 pubmed publisher..Our findings demonstrate the importance of Gpr177 in Wnt1-mediated development of the mouse embryo, suggesting an overlapping function of Wnt family members in the Wnt1-expressing cells. ..
- Chong Z, Hou J, Shang Y, Wang S, Maiese K. EPO relies upon novel signaling of Wnt1 that requires Akt1, FoxO3a, GSK-3?, and ?-catenin to foster vascular integrity during experimental diabetes. Curr Neurovasc Res. 2011;8:103-20 pubmed
- Jang J, Boxer R, Chodosh L. Isoform-specific ras activation and oncogene dependence during MYC- and Wnt-induced mammary tumorigenesis. Mol Cell Biol. 2006;26:8109-21 pubmed
- Chong Z, Li F, Maiese K. Cellular demise and inflammatory microglial activation during beta-amyloid toxicity are governed by Wnt1 and canonical signaling pathways. Cell Signal. 2007;19:1150-62 pubmed..and microglial activation, since these neuroprotective attributes of Wnt1 are lost during gene silencing of Wnt1 protein expression. Intimately tied to Wnt1 protection is the presence and activation of Akt1...
- Galli L, Barnes T, Secrest S, Kadowaki T, Burrus L. Porcupine-mediated lipid-modification regulates the activity and distribution of Wnt proteins in the chick neural tube. Development. 2007;134:3339-48 pubmed..These findings highlight the importance of porcupine-mediated lipid modifications in the formation of vertebrate Wnt activity gradients. ..
- Oguma K, Oshima H, Aoki M, Uchio R, Naka K, Nakamura S, et al. Activated macrophages promote Wnt signalling through tumour necrosis factor-alpha in gastric tumour cells. EMBO J. 2008;27:1671-81 pubmed publisher..These results suggest that macrophage-derived TNF-alpha promotes Wnt/beta-catenin signalling through inhibition of GSK3beta, which may contribute to tumour development in the gastric mucosa. ..
- Svirshchevskaya E, Mariotti J, Wright M, Viskova N, Telford W, Fowler D, et al. Rapamycin delays growth of Wnt-1 tumors in spite of suppression of host immunity. BMC Cancer. 2008;8:176 pubmed publisher..Rapamycin has a direct anti-tumor effect on Wnt-1 breast cancer in vivo that involves inhibition of the mTOR pathway at doses that also suppress host immune responses. ..
- Baena Lopez L, Garcia Bellido A. Control of growth and positional information by the graded vestigial expression pattern in the wing of Drosophila melanogaster. Proc Natl Acad Sci U S A. 2006;103:13734-9 pubmed..Our observations provide evidence that local cell interactions, triggered by differences in vestigial expression between neighboring cells, confer positional values operating in the control of growth and shape of the wing. ..
- Guo C, Qiu H, Huang Y, Chen H, Yang R, Chen S, et al. Lmx1b is essential for Fgf8 and Wnt1 expression in the isthmic organizer during tectum and cerebellum development in mice. Development. 2007;134:317-25 pubmed
- Cho R, Wang X, Diehn M, Shedden K, Chen G, Sherlock G, et al. Isolation and molecular characterization of cancer stem cells in MMTV-Wnt-1 murine breast tumors. Stem Cells. 2008;26:364-71 pubmed..These studies suggest that there is a cancer stem cell compartment in the MMTV-Wnt-1 murine breast tumor and that there is a clinical utility of this model for the study of cancer stem cells. ..
- Jessen S, Gu B, Dai X. Pygopus and the Wnt signaling pathway: a diverse set of connections. Bioessays. 2008;30:448-56 pubmed publisher..We further analyze the roles of the two conserved domains of Pygopus proteins in transcription, and propose a model for the molecular mechanism of Pygopus function in both Wg/Wnt signaling and Wnt-independent transcriptional regulation. ..
- Ataman B, Ashley J, Gorczyca D, Gorczyca M, Mathew D, Wichmann C, et al. Nuclear trafficking of Drosophila Frizzled-2 during synapse development requires the PDZ protein dGRIP. Proc Natl Acad Sci U S A. 2006;103:7841-6 pubmed..These results provide a mechanism by which DFz2 is transported from the postsynaptic membrane to the postsynaptic nucleus during synapse formation and implicate dGRIP as an essential molecule in the transport of this signal. ..