Cisplatin-selected resistance is associated with increased motility and stem-like properties via activation of STAT3/Snail axis in atypical teratoid/rhabdoid tumor cells

Wei Hsiu Liu, Ming Teh Chen, Mong Lien Wang, Yi Yen Lee, Guang-Yuh Chiou, Chian Shiu Chien, Pin I. Huang, Yi Wei Chen, Ming Chao Huang, Shih Hwa Chiou, Yang Hsin Shih, Hsin I. Ma*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

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 drugresistant but also increasingly oncogenic (invasion, EMT and recurrence). Therefore, the STAT3/Snail could be a target for ATRT treatment.

Original languageEnglish
Pages (from-to)1750-1768
Number of pages19
JournalOncotarget
Volume6
Issue number3
DOIs
StatePublished - 1 Jan 2015

Keywords

  • Atypical teratoid/rhabdoid tumor (ATRT)
  • Oncogenic resistance and cisplatin
  • Snail
  • STAT3

Fingerprint Dive into the research topics of 'Cisplatin-selected resistance is associated with increased motility and stem-like properties via activation of STAT3/Snail axis in atypical teratoid/rhabdoid tumor cells'. Together they form a unique fingerprint.

Cite this