Dishevelled 2 signaling promotes self-renewal and tumorigenicity in human gliomas Journal Article
| Authors: | Pulvirenti, T.; Van Der Heijden, M.; Droms, L. A.; Huse, J. T.; Tabar, V.; Hall, A. |
| Article Title: | Dishevelled 2 signaling promotes self-renewal and tumorigenicity in human gliomas |
| Abstract: | Glioblastoma multiforme is the most common glioma variant in adults and is highly malignant. Tumors are thought to harbor a subpopulation of stem-like cancer cells, with the bulk resembling neural progenitor-like cells that are unable to fully differentiate. Although multiple pathways are known to be involved in glioma tumorigenesis, the role of Wnt signaling has been poorly described. Here, we show that Dishevelled 2 (Dvl2), a key component of the Wnt signaling pathway, is overexpressed in human gliomas. RNA interference-mediated depletion of Dvl2 blocked proliferation and promoted the differentiation of cultured human glioma cell lines and primary, patient-derived glioma cells. In addition, Dvl2 depletion inhibited tumor formation after intracranial injection of glioblastoma cells in immunodeficient mice. Inhibition of canonical Wnt/β-catenin signaling also blocked proliferation, but unlike Dvl2 depletion, did not induce differentiation. Finally, Wnt5a, a noncanonical Wnt ligand, was also required for glioma cell proliferation. The data therefore suggest that both canonical and noncanonical Wnt signaling pathways downstream of Dvl2 cooperate to maintain the proliferative capacity of human glioblastomas. ©2011 AACR. |
| Keywords: | signal transduction; controlled study; protein expression; human cell; proto-oncogene proteins; nonhuman; glioma; brain neoplasms; cell proliferation; animal cell; mouse; animals; mice; animal tissue; protein depletion; animal experiment; animal model; rna interference; cell renewal; cell differentiation; mice, scid; cell line, tumor; cell transformation, neoplastic; cancer inhibition; glioma cell; glioblastoma; cell growth processes; carcinogenicity; ligand; adaptor proteins, signal transducing; phosphoproteins; immune deficiency; mice, inbred nod; wnt proteins; beta catenin; wnt protein; wnt5a protein; dishevelled 2; wnt signaling pathway |
| Journal Title: | Cancer Research |
| Volume: | 71 |
| Issue: | 23 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2011-12-01 |
| Start Page: | 7280 |
| End Page: | 7290 |
| Language: | English |
| DOI: | 10.1158/0008-5472.can-11-1531 |
| PROVIDER: | scopus |
| PMCID: | PMC3228897 |
| PUBMED: | 21990322 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 January 2012" - "CODEN: CNREA" - "Source: Scopus" |
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