FOXQ1 promotes gastric cancer metastasis through upregulation of Snail

Zhang,Jing; Liu,Yimin; Zhang,Jia; Cui,Xiaohai; Li,Gang; Wang,Jiansheng; Ren,Hong; Zhang,Yunfeng

doi:10.3892/or.2016.4736

FOXQ1 promotes gastric cancer metastasis through upregulation of Snail

Authors:
- Jing Zhang
- Yimin Liu
- Jia Zhang
- Xiaohai Cui
- Gang Li
- Jiansheng Wang
- Hong Ren
- Yunfeng Zhang
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Affiliations: The Second Department of Thoracic Surgery, First Afﬁliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Baoji Renmin Hospital, Baoji, Shaanxi 721000, P.R. China
Published online on: April 8, 2016 https://doi.org/10.3892/or.2016.4736
Pages: 3607-3613

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Abstract

Gastric cancer (GC) is one of the most common cancers, and the second most common cause of cancer deaths worldwide. Forkhead box Q1 (FOXQ1) is a member of the forkhead transcription factor family and its upregulation is closely correlated with tumor progression and prognosis of multiple cancer types, including GC. FOXQ1 has been shown to regulate EMT and function in human cancers. However, the role of FOXQ1 in regulating EMT in GC and the exactly mechanism has not been clarified. The purpose of this study was to investigate the effects of FOXQ1 on EMT in human GC. FOXQ1 protein was detected by immunohistochemistry in human GC specimens and their clinical significance evaluated. We examined the cell biology and molecular biology changes after overexpression and knockdown of FOXQ1 in gastric cancer cells in vitro. To further understand the underlying mechanisms of EMT promoted by FOXQ1, we examined the changes of target genes of FOXQ1 after overexpression and knockdown of FOXQ1 in gastric cancer cells. In the present study, we demonstrate that FOXQ1 is overexpressed in GC tissues and its expression level is closely correlated with histologic differentiation, pTNM stage, and lymphatic metastasis of GC. Kaplan-Meier survival analysis showed that a high expression level of FOXQ1 resulted in a significantly poor prognosis of GC patients. FOXQ1 modulated GC cell invasion in vitro, and induced E-cadherin repression. FOXQ1 also upregulated the expression of vimentin in vitro. The Snail signaling pathway was likely involved in the induction of EMT by FOXQ1 in GC. Our results demonstrate that FOXQ1 is a prognostic marker for patients with GC, FOXQ1 overexpression is involved in acquisition of the mesenchymal phenotype of gastric cancer cells, and that subsequent Snail expression is essential for induction of EMT. The results suggest that FOXQ1 is a potential therapeutic target for the development of therapies for GC.

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