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

16 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

Fingerprint

Catenins
Colorectal Neoplasms
Neoplasms
Survival
Heterografts
Colonic Neoplasms
Veins
Clone Cells
Western Blotting

ASJC Scopus subject areas

  • General

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

DDX3 promotes tumor invasion in colorectal cancer via the CK1ε/Dvl2 axis. / He, Tsung Ying; Wu, De Wei; Lin, Po Lin; Wang, Lee; Huang, Chi Chou; Chou, Ming Chih; Lee, Huei.

In: Scientific Reports, Vol. 6, 21483, 19.02.2016.

Research output: Contribution to journalArticle

He, TY, Wu, DW, Lin, PL, Wang, L, Huang, CC, Chou, MC & Lee, H 2016, 'DDX3 promotes tumor invasion in colorectal cancer via the CK1ε/Dvl2 axis', Scientific Reports, vol. 6, 21483. https://doi.org/10.1038/srep21483
He, Tsung Ying ; Wu, De Wei ; Lin, Po Lin ; Wang, Lee ; Huang, Chi Chou ; Chou, Ming Chih ; Lee, Huei. / DDX3 promotes tumor invasion in colorectal cancer via the CK1ε/Dvl2 axis. In: Scientific Reports. 2016 ; Vol. 6.
@article{029620d528af48859f15c08e9bea7c23,
title = "DDX3 promotes tumor invasion in colorectal cancer via the CK1ε/Dvl2 axis",
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.",
author = "He, {Tsung Ying} and Wu, {De Wei} and Lin, {Po Lin} and Lee Wang and Huang, {Chi Chou} and Chou, {Ming Chih} and Huei Lee",
year = "2016",
month = "2",
day = "19",
doi = "10.1038/srep21483",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - DDX3 promotes tumor invasion in colorectal cancer via the CK1ε/Dvl2 axis

AU - He, Tsung Ying

AU - Wu, De Wei

AU - Lin, Po Lin

AU - Wang, Lee

AU - Huang, Chi Chou

AU - Chou, Ming Chih

AU - Lee, Huei

PY - 2016/2/19

Y1 - 2016/2/19

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84959019020&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959019020&partnerID=8YFLogxK

U2 - 10.1038/srep21483

DO - 10.1038/srep21483

M3 - Article

C2 - 26892600

AN - SCOPUS:84959019020

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 21483

ER -