DIXDC1 increases the invasion and migration ability of non‐small‐cell lung cancer cells via the PI3K‐AKT/AP‐1 pathway. Issue 11 (29th June 2013)

• Record Type: Journal Article
• Authors: Xu, Zhonghai; Liu, Di; Fan, Chuifeng; Luan, Lan; Zhang, Xiupeng; Wang, Enhua
• Is Part Of: Molecular carcinogenesis. Volume 53:Issue 11(2014:Nov.)
• Page Start: 917
• Page End: 925
• Publication Date: 2013-06-29
• Subjects: Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22059
• Languages: English
• ISSNs: 0899-1987

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="mc22059-sec-0001" sec-type="section"> <p>DIX domain containing 1 (DIXDC1), is a human homolog of Ccd1, a recently identified DIX domain containing protein in zebrafish. DIXDC1 protein was detected in human colorectal adenocarcinoma tissues and was found to be correlated with a high cell proliferation index. We demonstrated DIXDC1 overexpression in 55% (92/167) of non‐small cell lung cancer (NSCLC) cases, compared to adjacent noncancerous lung tissues (<italic>P</italic> &lt; 0.01). Overexpression of DIXDC1 was associated with lymph node metastasis and more advanced TNM stage (<italic>P</italic> &lt; 0.001 and <italic>P</italic> = 0.001, respectively). Kaplan–Meier survival curves and log‐rank testing indicated that overexpression of DIXDC1 correlated with worse overall survival in NSCLC (<italic>P</italic> = 0.031). DIXDC1 was more abundant in seven NSCLC lines than the bronchial cell line HBE, and modulation of its expression regulated AP‐1 activity; MMP2, MMP7, and MMP9 protein and mRNA; and invasion ability. Metalloproteinase induction was reversed by PI3K/AKT and AP‐1 inhibition. These results suggest DIXDC1 is associated with stage and prognosis in NSCLC, and may promote invasion and migration through PI3K‐AKT/AP‐1‐dependent activation of metalloproteinases. © 2013 Wiley Periodicals, Inc. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>