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NT5DC2 promotes tumorigenicity of glioma stem-like cells by upregulating fyn.

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.

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  • Authors+Show Affiliations

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    State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.

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    State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.

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    State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.

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    State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.

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    State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.

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    State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.

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    State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.

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    State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.

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    State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.

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    State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.

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    State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, Beijing, 100850, China.

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    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.

    Source

    Cancer letters 454: 2019 Jul 10 pg 98-107

    Pub Type(s)

    Journal Article

    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., ... Man, J. (2019). NT5DC2 promotes tumorigenicity of glioma stem-like cells by upregulating fyn. Cancer Letters, 454, pp. 98-107. doi: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 Jul 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 -