Maintenance of tumor initiating cells of defined genetic composition by nucleostemin
Name
Okamoto-2011-Maintenance of tumor.pdf
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1.29 MB
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Author(s)
Okamoto, Naoko
Yasukawa, Mami
Nguyen, Christine
Kasim, Vivi
Maida, Yoshiko
Possemato, Richard
Shibata, Tatsuhiro
Ligon, Keith L.
Fukami, Kiyoko
Hahn, William C.
Date Issued
July 2011
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Citation
Okamato, N. et al. "Maintenance of tumor initiating cells of defined genetic composition by nucleostemin." Proceedings of the National Academy of Sciences 108.51 (2011): 20388–20393. Copyright ©2011 by the National Academy of Sciences
Version
Final published version
Abstract
Recent work has identified a subset of cells resident in tumors that exhibit properties similar to those found in normal stem cells. Such cells are highly tumorigenic and may be involved in resistance to treatment. However, the genes that regulate the tumor initiating cell (TIC) state are unknown. Here, we show that overexpression of either of the nucleolar GTP-binding proteins nucleostemin (NS) or GNL3L drives the fraction of genetically defined tumor cells that exhibit markers and tumorigenic properties of TICs. Specifically, cells that constitutively express elevated levels of NS or GNL3L exhibit increased TWIST expression, phosphorylation of STAT3, expression of genes that induce pluripotent stem cells, and enhanced radioresistance; in addition, they form tumors even when small numbers of cells are implanted and exhibit an increased propensity to metastasize. GNL3L/NS forms a complex with the telomerase catalytic subunit [human telomerase reverse transcriptase (hTERT)] and the SWItch-Sucrose NonFermentable (SWI-SNF) complex protein brahma-related gene 1 (BRG1), and the expression of each of these components is necessary to facilitate the cancer stem cell state. Together, these observations define a complex composed of TERT, BRG1, and NS/GNL3L that maintains the function of TICs.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1073/pnas.1015171108
