DDX3 promotes tumor invasion in colorectal cancer via the CK1ε/Dvl2 axis

Tsung Ying He, De Wei Wu, Po Lin Lin, Lee Wang, Chi Chou Huang, Ming Chih Chou, Huei Lee

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

DDX3, a subunit of CK1ε, phosphorylates Dvl2 to promote β-catenin activation. Overexpression of the Dvl2 protein results in potent activation of β-catenin/TCF signaling in colorectal cancer. Therefore, we hypothesized that DDX3 might promote tumor invasion via the CK1ε/Dvl2 axis due to β-catenin/TCF activation. Western blotting showed that β-catenin expression was decreased by DDX3 knockdown and increased by DDX3 overexpression in colorectal cancer cells. The TCF promoter activity and invasion capability were concomitantly increased and decreased by DDX3 manipulation in these cells. The invasion capability in colon cancer cells and xenograft lung tumor nodules induced by a DDX3-overexpressing T84 stable clone in tail-vein injection model were nearly suppressed by inhibitors of CK1ε (PF4800567) and β-catenin/TCF signaling (XAV939). Among colorectal cancer patients, DDX3 expression was positively correlated with the expression of pDvl2 and nuclear β-catenin in tumor tissues. The expression of pDvl2 occurred more frequently in high-nuclear than in low-nuclear β-catenin tumors. A prognostic significance of DDX3, pDvl2, and nuclear β-catenin on overall survival and relapse free survival was observed in this study population. We therefore suggest CK1ε or β-catenin/TCF signaling as potential targets for improving tumor regression and outcomes in colorectal cancer, particularly tumors with high-DDX3/high-nuclear β-catenin or high-DDX3/high-pDvl2/high-nuclear β-catenin expression.

Original languageEnglish
Article number21483
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Feb 19 2016

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'DDX3 promotes tumor invasion in colorectal cancer via the CK1ε/Dvl2 axis'. Together they form a unique fingerprint.

  • Cite this

    He, T. Y., Wu, D. W., Lin, P. L., Wang, L., Huang, C. C., Chou, M. C., & Lee, H. (2016). DDX3 promotes tumor invasion in colorectal cancer via the CK1ε/Dvl2 axis. Scientific Reports, 6, [21483]. https://doi.org/10.1038/srep21483