GDF15 promotes glioma stem cell-like phenotype via regulation of ERK1/2-c-Fos-LIF signaling

被引:27
作者
Zhu, Shan [1 ]
Yang, Ning [1 ]
Guan, Yi [2 ]
Wang, Xue [1 ]
Zang, Guoxia [1 ]
Lv, Xinping [1 ]
Deng, Shuanglin [2 ]
Wang, Wan [1 ]
Li, Tete [1 ]
Chen, Jingtao [1 ]
机构
[1] First Hosp Jilin Univ, Inst Translat Med, Changchun, Peoples R China
[2] First Hosp Jilin Univ, Dept Neurosurg, Changchun, Peoples R China
基金
中国国家自然科学基金;
关键词
LEUKEMIA INHIBITORY FACTOR; SELF-RENEWAL; CANCER-CELLS; PROSTATE-CANCER; DENDRITIC CELLS; GROWTH; PROLIFERATION; GLIOBLASTOMA; EXPRESSION; IMIQUIMOD;
D O I
10.1038/s41420-020-00395-8
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Growth differentiation factor 15 (GDF15), a member of the transforming growth factor beta family, is associated with tumor progression, metastasis, and cell apoptosis. However, controversy persists regarding the role of GDF15 in different tumor types, and its function in glioma stem cells (GSCs) remains unknown. Here, we report that GDF15 promotes the GSC-like phenotype in GSC-like cells (GSCLCs) through the activation of leukemia inhibitor factor (LIF)-STAT3 signaling. Mechanistically, GDF15 was found to upregulate expression of the transcription factor c-Fos, which binds to the LIF promoter, leading to enhanced transcription of LIF in GSCLCs. Furthermore, GDF15 may activate the ERK1/2 signaling pathway in GSCLCs, and the upregulation of LIF expression and the GSC-like phenotype was dependent on ERK1/2 signaling. In addition, the small immunomodulator imiquimod induced GDF15 expression, which in turn activated the LIF-STAT3 pathway and subsequently promoted the GSC-like phenotype in GSCLCs. Thus, our results demonstrate that GDF15 can act as a proliferative and pro-stemness factor for GSCs, and therefore, it may represent a potential therapeutic target in glioma treatment.
引用
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页数:12
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