Upregulation of DACT2 suppresses proliferation and enhances apoptosis of glioma cell via inactivation of YAP signaling pathway

作者：Tan, Ying; Li, Qiu-Meng; Huang, Ning; Cheng, Si; Zhao, Guan-Jian; Chen, Hong; Chen, Song; Tang, Zhao-Hua; Zhang, Wen-Qian; Huang, Qin; Cheng, Yuan^*

来源：Cell Death & Disease, 2017, 8(8): e2981.

DOI：10.1038/cddis.2017.385

• YES-ASSOCIATED PROTEIN
• BREAST-CANCER
• TUMOR-SUPPRESSOR
• HIPPO PATHWAY
• CANDIDATE ONCOGENE
• THERAPEUTIC TARGET
• GASTRIC-CANCER
• METHYLATION
• GENE
• TAZ

DACT2, one of the Dact gene family members, was shown to function as a tumor suppressor. However, its function in gliomas remains largely unknown. In this study, we investigated the role of DACT2, underlying molecular mechanisms and its clinical significance in glioma patients. Downexpression of DACT2 in gliomas compared with adjacent normal brain tissues was correlated with glioma grade and poor survival. Cox regression analysis revealed that the DACT2 is an independent prognostic indicator for glioma patients. Overexpression of DACT2 in glioma cells inhibited proliferation, cell cycle and enhanced apoptosis, sensitivity to temozolomide in vitro and suppressed tumor growth in vivo. Whereas knockdown of DACT2 induce opposite reaction. Mechanistically, overexpression of DACT2 resulted in upregulation of important signaling molecules such as p-YAP and p-beta-catenin, and prevent YAP translocating into nucleus and sequestering in the cytoplasm to degrade. The study further proved that DACT2 can suppress YAP through Wnt/beta-catenin signaling pathway. Collectively, these data indicate that DACT2 has a tumor suppressor function via inactivation of YAP pathway, providing a promising target for the treatment of gliomas.

• 出版日期2017-8
• 单位重庆医科大学