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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Pizzo, Donald P. Chen, Clark C. Kushwaha, Deepa S. Kozono, David Mao, Ying Zhu, Kaya Sampetrean, Oltea Harismendy, Olivier Vandenberg, Scott R. Saya, Hideyuki Matsui, Hiroko Li, Jie Ramakrishnan, Valya Nakano, Ichiro Merzon, Dmitry Zhu, Shan Hua, Wei Kwon, Chang-hyuk Nitta, Masayuki Gonda, David |
| Description | Author Affiliation: Kozono D ( Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215); Li J ( Division of Neurosurgery, University of California, San Diego, La Jolla, CA 92093); Nitta M ( Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215); Sampetrean O ( Division of Gene Regulation, Keio University School of Medicine, Tokyo 160-8582, Japan); Gonda D ( Division of Neurosurgery, University of California, San Diego, La Jolla, CA 92093); Kushwaha DS ( Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215); Merzon D ( Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215); Ramakrishnan V ( Division of Neurosurgery, University of California, San Diego, La Jolla, CA 92093); Zhu S ( Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215); Zhu K ( Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02215); Matsui H ( Department of Pediatrics and Rady Children's Hospital, University of California, San Diego, La Jolla, CA 92093); Harismendy O ( Department of Pediatrics and Rady Children's Hospital, University of California, San Diego, La Jolla, CA 92093); Hua W ( Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China); Mao Y ( Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China); Kwon CH ( Department of Neurological Surgery, Ohio State University Medical Center, Columbus, OH 43210); Saya H ( Division of Gene Regulation, Keio University School of Medicine, Tokyo 160-8582, Japan); Nakano I ( Department of Neurological Surgery, Ohio State University Medical Center, Columbus, OH 43210); Pizzo DP ( Department of Pathology, University of California, San Diego, La Jolla, CA 92037.); VandenBerg SR ( Department of Pathology, University of California, San Diego, La Jolla, CA 92037.); Chen CC ( Division of Neurosurgery, University of California, San Diego, La Jolla, CA 92093); |
| Abstract | The available evidence suggests that the lethality of glioblastoma is driven by small subpopulations of cells that self-renew and exhibit tumorigenicity. It remains unclear whether tumorigenicity exists as a static property of a few cells or as a dynamically acquired property. We used tumor-sphere and xenograft formation as assays for tumorigenicity and examined subclones isolated from established and primary glioblastoma lines. Our results indicate that glioblastoma tumorigenicity is largely deterministic, yet the property can be acquired spontaneously at low frequencies. Further, these dynamic transitions are governed by epigenetic reprogramming through the lysine-specific demethylase 1 (LSD1). LSD depletion increases trimethylation of histone 3 lysine 4 at the avian myelocytomatosis viral oncogene homolog (MYC) locus, which elevates MYC expression. MYC, in turn, regulates oligodendrocyte lineage transcription factor 2 (OLIG2), SRY (sex determining region Y)-box 2 (SOX2), and POU class 3 homeobox 2 (POU3F2), a core set of transcription factors required for reprogramming glioblastoma cells into stem-like states. Our model suggests epigenetic regulation of key transcription factors governs transitions between tumorigenic states and provides a framework for glioblastoma therapeutic development. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 30 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Brain Neoplasms Metabolism Epigenesis, Genetic Gene Expression Regulation, Neoplastic Glioblastoma Histone Demethylases Proto-Oncogene Proteins C-myc Animals Cell Line, Tumor Cell Transformation, Neoplastic Gene Expression Profiling Gene Silencing Mice Mice, Inbred C57BL Neoplasm Transplantation Neoplasms Stochastic Processes Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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