DDX3 enhances oncogenic KRAS-induced tumor invasion in colorectal cancer via the β-catenin/ZEB1 axis

De Wei Wu, Po Lin Lin, Ya Wen Cheng, Chi Chou Huang, Lee Wang, Huei Lee

研究成果: 雜誌貢獻文章同行評審

30 引文 斯高帕斯(Scopus)

摘要

DDX3 plays a dual role in colorectal cancer; however, the role and underlying mechanism of DDX3 in colorectal tumorigenesis remains unclear. Here, we provide evidence that DDX3 enhances oncogenic KRAS transcription via an increase in SP1 binding to its promoter. Accelerating oncogenic KRAS expression by DDX3 promotes the invasion capability via the ERK/PTEN/AKT/β-catenin cascade. Moreover, the β-catenin/ZEB1 axis is responsible for DDX3-induced cell invasiveness and xenograft lung tumor nodule formation. The xenograft lung tumor nodules induced by DDX3-overexpressing T84 stable clone were nearly suppressed by the inhibitor of AKT (perifosine) or β-catenin (XAV939). Among patients, high KRAS, positive nuclear β-catenin expression and high ZEB1 were more commonly occurred in high-DDX3 tumors than in low-DDX3 tumors. High-DDX3, high-KRAS, positive nuclear β-catenin tumors, and high-ZEB1 exhibited worse overall survival (OS) and relapse free survival (RFS) than their counterparts. In conclusion, DDX3 may play an oncogenic role to promote tumor growth and invasion in colon cancer cells via the β-catenin/ZEB1 axis due to increasing KRAS transcription. We therefore suggest that AKT or β-catenin may potentially act as a therapeutic target to improve tumor regression and outcomes in colorectal cancer patients who harbored high-DDX3 tumors.
原文英語
頁(從 - 到)22687-22699
頁數13
期刊Oncotarget
7
發行號16
DOIs
出版狀態已發佈 - 四月 19 2016

ASJC Scopus subject areas

  • 腫瘤科

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