title: DIXDC1 activates the Wnt signaling pathway and promotes gastric cancer cell invasion and metastasis.
abstract: 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.
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Cong
authors: C
authors: Tan
authors: Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: Fan
authors: F
authors: Qiao
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Ping
authors: P
authors: Wei
authors: Cancer institute, Fudan University Shanghai Cancer Center, Shanghai, China.
authors: Yayun
authors: Y
authors: Chi
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Weige
authors: W
authors: Wang
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Shujuan
authors: S
authors: Ni
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Qifeng
authors: Q
authors: Wang
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Tongzhen
authors: T
authors: Chen
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Weiqi
authors: W
authors: Sheng
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Xiang
authors: X
authors: Du
authors: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors: Lei
authors: L
authors: Wang
mesh_terms: D015820:Cadherins / Q000032:analysis / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis* / Q000378:metabolism*; D008297:Male; D008840:Microfilament Proteins / Q000032:analysis* / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000473:pathology; D011379:Prognosis; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000032:analysis / Q000378:metabolism
chemical_list: D015820:Cadherins; C513335:DIXDC1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D051176:beta Catenin
keywords: DIXDC1; gastric cancer; invasion; migration; the Wnt signaling pathway