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

Scientific Reports
Tsung-Ying HeHuei Lee

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 ther...Continue Reading

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Citations

Oct 27, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Abdul Salam KhanAli Moshfegh
Feb 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marina K KukhanovaAlexander V Ivanov
Jan 27, 2017·Journal of the National Cancer Institute·Wanpei CaiAlan Prem Kumar
Feb 23, 2017·Cellular and Molecular Life Sciences : CMLS·Liangmei HeZhiping Liu
Jan 25, 2020·Apoptosis : an International Journal on Programmed Cell Death·Omprakash ShriwasRupesh Dash
Jun 27, 2019·Proceedings of the National Academy of Sciences of the United States of America·Hongyu GuanMengfeng Li
Oct 1, 2020·World Journal of Gastroenterology : WJG·Noémie LegrandCyril Sobolewski
Sep 10, 2020·International Journal of Molecular Sciences·Bartolo BonoGiovanni Maga
Feb 26, 2021·Molecular Cancer·Jie MoBixiang Zhang
Aug 14, 2020·Journal of Medicinal Chemistry·Valentina RivaGiovanni Maga

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Methods Mentioned

BETA
ubiquitination
transfections
transfection
xenograft
electrophoresis

Software Mentioned

SPSS

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