標題: Cisplatin-selected resistance is associated with increased motility and stem-like properties via activation of STAT3/Snail axis in atypical teratoid/rhabdoid tumor cells
作者: Liu, Wei-Hsiu
Chen, Ming-Teh
Wang, Mong-Lien
Lee, Yi-Yen
Chiou, Guang-Yuh
Chien, Chian-Shiu
Huang, Pin-I
Chen, Yi-Wei
Huang, Ming-Chao
Chiou, Shih-Hwa
Shih, Yang-Hsin
Ma, Hsin-I
生物科技學院
College of Biological Science and Technology
關鍵字: Atypical teratoid/rhabdoid tumor (ATRT);STAT3;Snail;oncogenic resistance and cisplatin
公開日期: 30-Jan-2015
摘要: Atypical teratoid/rhabdoid tumor (ATRT) is a malignant pediatric brain tumor with great recurrence after complete surgery and chemotherapy. Here, we demonstrate that cisplatin treatment selects not only for resistance but also for a more oncogenic phenotype characterized by high self-renewal and invasive capabilities. These phenomena are likely due to STAT3 upregulatoin which occurred simultaneously with higher expression of Snail, an activator of epithelial-mesenchymal transition (EMT), in ATRT-CisR cells. STAT3 knockdown effectively suppressed Snail expression and blocked motility and invasion in ATRT-CisR cells, while overexpressing Snail reversed these effects. Chromatin immunoprecipitation assay indicated that STAT3 directly bound to Snail promoter. Moreover, STAT3 knockdown effectively suppressed cancer stem-like properties, synergistically enhanced the chemotherapeutic effect, and significantly improved survival rate in ATRT-CisR-transplanted immunocompromised mice. Finally, immunohistochemistrical analysis showed that STAT3 and Snail were coexpressed at high levels in recurrent ATRT tissues. Thus, the STAT3/Snail pathway plays an important role in oncogenic resistance, rendering cells not only drug-resistant but also increasingly oncogenic (invasion, EMT and recurrence). Therefore, the STAT3/Snail could be a target for ATRT treatment.
URI: http://hdl.handle.net/11536/124717
ISSN: 1949-2553
期刊: ONCOTARGET
起始頁: 1750
結束頁: 1768
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