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

摘要: // Wei-Hsiu Liu 1, 2 , Ming-Teh Chen 3, 4, * Mong-Lien Wang 5 Yi-Yen Lee 5, 7, Guang-Yuh Chiou 6 Chian-Shiu Chien 9 Pin-I Huang 8 Yi-Wei Ming-Chao 7 Shih-Hwa Yang-Hsin Shih 4 Hsin-I Ma 1 Graduate Institute of Medical Sciences, National Defense Center, Taipei, Taiwan Department Neurological Surgery, Tri-Service General Hospital and 3 School Medicine, Yang-Ming University, Neurosurgery, Institute, Taipei Veterans & Clinical College Biological Science Technology, Chiao Tung Univeristy, Division Pediatric Hospital, Cancer Research Education, These authors have contributed equally to this work Correspondence to: Ma, e-mail: uf004693@mail2000.com.tw Keywords: Atypical teratoid/rhabdoid tumor (ATRT), STAT3, Snail, oncogenic resistance cisplatin Received: August 24, 2014      Accepted: November 11, Published: January 31, 2015 ABSTRACT (ATRT) is a malignant pediatric brain with great recurrence after complete surgery chemotherapy. Here, we demonstrate that treatment selects not only for but also more phenotype characterized by high self-renewal invasive capabilities. phenomena are likely due STAT3 upregulatoin which occurred simultaneously higher expression an activator epithelial–mesenchymal transition (EMT), in ATRT-CisR cells. knockdown effectively suppressed Snail blocked motility invasion cells, while overexpressing reversed these effects. Chromatin immunoprecipitation assay indicated directly bound promoter. Moreover, cancer stem-like properties, synergistically enhanced the chemotherapeutic effect, significantly improved survival rate ATRT-CisR-transplanted immunocompromised mice. Finally, immunohistochemistrical analysis showed were coexpressed at levels recurrent ATRT tissues. Thus, STAT3/Snail pathway plays important role resistance, rendering cells drug-resistant increasingly (invasion, EMT recurrence). Therefore, could be target treatment.