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NT5DC2 promotes tumorigenicity of glioma stem-like cells by upregulating fyn.
Cancer Lett. 2019 07 10; 454:98-107.CL

Abstract

Glioblastoma (GBM) is an incurable primary brain tumor that is highly resistant to current treatments. Glioma stem-like cells (GSCs) are an aggressive population of glioma cells that not only initiate malignant growth, but also promote therapeutic resistance. Thus, targeting GSCs is critical for improving GBM treatment and ensuring complete eradication of the tumor. Here, we show that NT5DC2 (5'-Nucleotidase Domain Containing 2), a functionally unknown protein, plays a crucial role in GSC tumor initiation via upregulating Fyn expression. NT5DC2 is preferentially expressed in GSCs relative to the non-stem tumor cells. Knockdown of NT5DC2 significantly inhibits the GSC tumorsphere formation and cell viability in vitro, and tumorigenesis in vivo, thus, prolonging animal survival. Moreover, disruption of NT5DC2 in GSCs markedly reduces the expression of Fyn, a Src family proto-oncogene that has been implicated in the regulation of GBM progression. Importantly, the expression of NT5DC2 strongly correlated with increased aggression of human gliomas, but not that of other brain tumors. Taken together, our results uncover the function of NT5DC2 in GSC maintenance and highlight NT5DC2 as a promising therapeutic target for GBM.

Authors+Show Affiliations

State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China. Electronic address: alli@ncba.ac.cn.State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China. Electronic address: jhman@ncba.ac.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30978441

Citation

Guo, Saisai, et al. "NT5DC2 Promotes Tumorigenicity of Glioma Stem-like Cells By Upregulating Fyn." Cancer Letters, vol. 454, 2019, pp. 98-107.
Guo S, Ran H, Xiao D, et al. NT5DC2 promotes tumorigenicity of glioma stem-like cells by upregulating fyn. Cancer Lett. 2019;454:98-107.
Guo, S., Ran, H., Xiao, D., Huang, H., Mi, L., Wang, X., Chen, L., Li, D., Zhang, S., Han, Q., Zhou, T., Li, A., & Man, J. (2019). NT5DC2 promotes tumorigenicity of glioma stem-like cells by upregulating fyn. Cancer Letters, 454, 98-107. https://doi.org/10.1016/j.canlet.2019.04.003
Guo S, et al. NT5DC2 Promotes Tumorigenicity of Glioma Stem-like Cells By Upregulating Fyn. Cancer Lett. 2019 07 10;454:98-107. PubMed PMID: 30978441.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NT5DC2 promotes tumorigenicity of glioma stem-like cells by upregulating fyn. AU - Guo,Saisai, AU - Ran,Haowen, AU - Xiao,Dake, AU - Huang,Haohao, AU - Mi,Lanjuan, AU - Wang,Xinzheng, AU - Chen,Lishu, AU - Li,Da, AU - Zhang,Songyang, AU - Han,Qiuying, AU - Zhou,Tao, AU - Li,Ailing, AU - Man,Jianghong, Y1 - 2019/04/10/ PY - 2018/12/20/received PY - 2019/03/24/revised PY - 2019/04/04/accepted PY - 2019/4/13/pubmed PY - 2019/4/13/medline PY - 2019/4/13/entrez KW - Fyn KW - Glioblastoma KW - Glioma Stem-like Cell KW - NT5DC2 KW - Tumorigenesis SP - 98 EP - 107 JF - Cancer letters JO - Cancer Lett. VL - 454 N2 - Glioblastoma (GBM) is an incurable primary brain tumor that is highly resistant to current treatments. Glioma stem-like cells (GSCs) are an aggressive population of glioma cells that not only initiate malignant growth, but also promote therapeutic resistance. Thus, targeting GSCs is critical for improving GBM treatment and ensuring complete eradication of the tumor. Here, we show that NT5DC2 (5'-Nucleotidase Domain Containing 2), a functionally unknown protein, plays a crucial role in GSC tumor initiation via upregulating Fyn expression. NT5DC2 is preferentially expressed in GSCs relative to the non-stem tumor cells. Knockdown of NT5DC2 significantly inhibits the GSC tumorsphere formation and cell viability in vitro, and tumorigenesis in vivo, thus, prolonging animal survival. Moreover, disruption of NT5DC2 in GSCs markedly reduces the expression of Fyn, a Src family proto-oncogene that has been implicated in the regulation of GBM progression. Importantly, the expression of NT5DC2 strongly correlated with increased aggression of human gliomas, but not that of other brain tumors. Taken together, our results uncover the function of NT5DC2 in GSC maintenance and highlight NT5DC2 as a promising therapeutic target for GBM. SN - 1872-7980 UR - https://www.unboundmedicine.com/medline/citation/30978441/NT5DC2_promotes_tumorigenicity_of_glioma_stem-like_cells_by_upregulating_fyn L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3835(19)30228-9 DB - PRIME DP - Unbound Medicine ER -