Open AccessDDX 5 promotes proliferation and tumorigenesis of non‐small‐cell lung cancer cells by activating β‐catenin signaling pathway
Author(s) -
Wang Zhendong,
Luo Zhonghua,
Zhou Lin,
Li Xiaofei,
Jiang Tao,
Fu Enqing
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12755
Subject(s) - cyclin d1 , cancer research , carcinogenesis , cell growth , downregulation and upregulation , wnt signaling pathway , catenin , gene silencing , biology , cancer , signal transduction , medicine , cell cycle , microbiology and biotechnology , biochemistry , genetics , gene
The DEAD ‐box‐protein DDX 5 is an ATP ‐dependent RNA helicase that is frequently overexpressed in various cancers and acts as a transcriptional co‐activator of several transcription factors, including β‐catenin. DDX 5 is reported to be involved in cancer progression by promoting cell proliferation and epithelial–mesenchymal transition. However, the clinical significance and biological role of DDX 5 in non‐small‐cell lung cancer ( NSCLC ) remain largely unknown. In this study, we examined the expression of DDX 5 in clinical NSCLC samples, investigated its role in regulating NSCLC cell proliferation and tumorigenesis, and explored the possible molecular mechanism. We found that DDX 5 was significantly overexpressed in NSCLC tissues as compared with the matched normal adjacent tissues. In addition, overexpression of DDX 5 was associated with advanced clinical stage, higher Ki67 index, and shorter overall survival in NSCLC patients. Upregulation of DDX 5 promoted proliferation of NSCLC cells in vitro and growth of NSCLC xenografts in vivo , whereas downregulation of DDX 5 showed the opposite effects. Furthermore, DDX 5 directly interacted with β‐catenin, promoted its nuclear translocation, and co‐activated the expression of cyclin D1 and c‐Myc. β‐catenin silencing significantly abrogated DDX 5‐induced cyclin D1 and c‐Myc expression and proliferation in NSCLC cells. Interestingly, DDX 5 and cyclin D1 expression followed positive correlation in the same set of NSCLC samples. These findings indicated that DDX 5 played an important role in the proliferation and tumorigenesis of NSCLC cells by activating the β‐catenin signaling pathway. Therefore, DDX 5 may serve as a novel prognostic marker and potential therapeutic target in the treatment of NSCLC .