DIXDC1 activates the Wnt signaling pathway and promotes gastric cancer cell invasion and metastasis

• Published in: Molecular carcinogenesis Vol. 55; no. 4; pp. 397 - 408
• Main Authors: Tan, Cong, Qiao, Fan, Wei, Ping, Chi, Yayun, Wang, Weige, Ni, Shujuan, Wang, Qifeng, Chen, Tongzhen, Sheng, Weiqi, Du, Xiang, Wang, Lei
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.04.2016; Wiley Subscription Services, Inc
• Subjects: beta Catenin - analysis; beta Catenin - metabolism; Cadherins - analysis; Cadherins - metabolism; Cell Line, Tumor; Cell Movement; DIXDC1; Female; Gastric cancer; Humans; Intracellular Signaling Peptides and Proteins - analysis; Intracellular Signaling Peptides and Proteins - metabolism; invasion; Male; Metastasis; Microfilament Proteins - analysis; Microfilament Proteins - metabolism; Middle Aged; migration; Neoplasm Invasiveness - pathology; Neoplasm Metastasis - pathology; Prognosis; Protein expression; Stomach - metabolism; Stomach - pathology; Stomach Neoplasms - diagnosis; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; the Wnt signaling pathway; Wnt Signaling Pathway; DIXDC1; migration; the Wnt signaling pathway; gastric cancer; invasion
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.22290

DIXDC1 (Dishevelled‐Axin domain containing 1) is a DIX (Dishevelled‐Axin) domain‐possessing protein that promotes colon cancer cell proliferation and increases the invasion and migration ability of non‐small‐cell lung cancer via the PI3K pathway. As a positive regulator of the Wnt/β‐catenin pathway, the biological role of DIXDC1 in human gastric cancer and the relationship between DIXDC1 and the Wnt pathway are unclear. In the current study, the upregulation of DIXDC1 was detected in gastric cancer and was associated with advanced TNM stage cancer, lymph node metastasis, and poor prognosis. We also found that the overexpression of DIXDC1 could promote the invasion and migration of gastric cancer cells. The upregulation of MMPs and the downregulation of E‐cadherin were found to be involved in the process. DIXDC1 enhanced β‐catenin nuclear accumulation, which activated the Wnt pathway. Additionally, the inhibition of β‐catenin in DIXDC1‐overexpressing cells reversed the metastasis promotion effects of DIXDC1. These results demonstrate that the expression of DIXDC1 is associated with poor prognosis of gastric cancer patients and that DIXDC1 promotes gastric cancer invasion and metastasis through the activation of the Wnt pathway; E‐cadherin and MMPs are also involved in this process. © 2015 Wiley Periodicals, Inc.