PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and gliomas Journal Article
| Authors: | Zheng, H.; Ying, H.; Wiedemeyer, R.; Yan, H.; Quayle, S. N.; Ivanova, E. V.; Paik, J. H.; Zhang, H.; Xiao, Y.; Perry, S. R.; Hu, J.; Vinjamoori, A.; Gan, B.; Sahin, E.; Chheda, M. G.; Brennan, C.; Wang, Y. A.; Hahn, W. C.; Chin, L.; DePinho, R. A. |
| Article Title: | PLAGL2 regulates Wnt signaling to impede differentiation in neural stem cells and gliomas |
| Abstract: | A hallmark feature of glioblastoma is its strong self-renewal potential and immature differentiation state, which contributes to its plasticity and therapeutic resistance. Here, integrated genomic and biological analyses identified PLAGL2 as a potent protooncogene targeted for amplification/gain in malignant gliomas. Enhanced PLAGL2 expression strongly suppresses neural stem cell (NSC) and glioma-initiating cell differentiation while promoting their self-renewal capacity upon differentiation induction. Transcriptome analysis revealed that these differentiation-suppressive activities are attributable in part to PLAGL2 modulation of Wnt/β-catenin signaling. Inhibition of Wnt signaling partially restores PLAGL2-expressing NSC differentiation capacity. The identification of PLAGL2 as a glioma oncogene highlights the importance of a growing class of cancer genes functioning to impart stem cell-like characteristics in malignant cells. © 2010 Elsevier Inc. All rights reserved. |
| Keywords: | signal transduction; controlled study; protein expression; unclassified drug; human cell; dna-binding proteins; nonhuman; protein function; protein analysis; animal cell; mouse; animals; mice; proto oncogene; gene amplification; signaling; nuclear protein; tumor differentiation; animal experiment; animal model; cell renewal; neural stem cell; cell differentiation; transcriptomics; carcinogenesis; transcription factors; cell transformation, neoplastic; rna-binding proteins; regulatory mechanism; glioblastoma; nucleotide sequence; stemcell; newborn; stem cells; cellcycle; wnt proteins; beta catenin; wnt protein; mitosis inhibition; protein plagl2 |
| Journal Title: | Cancer Cell |
| Volume: | 17 |
| Issue: | 5 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2010-05-18 |
| Start Page: | 497 |
| End Page: | 509 |
| Language: | English |
| DOI: | 10.1016/j.ccr.2010.03.020 |
| PUBMED: | 20478531 |
| PROVIDER: | scopus |
| PMCID: | PMC2900858 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 20 April 2011" - "CODEN: CCAEC" - "Source: Scopus" |
