Gastrin-17 induces gastric cancer cell epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway.

Affiliation

Li Y(1)(2), Zhao Y(1)(3), Li Y(1)(3), Zhang X(1)(3), Li C(1)(3), Long N(1)(3), Chen X(1)(3), Bao L(4), Zhou J(1)(3)(4), Xie Y(5)(6).
Author information:
(1)Key Laboratory of Endemic and Ethnic Diseases
(Guizhou Medical University), Ministry of Education, Guizhou, China.
(2)Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
(3)Key Laboratory of Medical Molecular Biology
(Guizhou Medical University), No. 9, Beijing Road, Guiyang, 550004, China.
(4)Affiliated Hospital, Guiyang Medical University, No. 9, Beijing Road, Guiyang, 550004, China.
(5)Key Laboratory of Endemic and Ethnic Diseases
(Guizhou Medical University), Ministry of Education, Guizhou, China. [Email]
(6)Key Laboratory of Medical Molecular Biology
(Guizhou Medical University), No. 9, Beijing Road, Guiyang, 550004, China. [Email]

Abstract

Gastric cancer (GC) is one of the most common cancers, with most patients often succumbing to death as a result of tumor metastasis. Recent work has demonstrated that gastrin is closely associated with GC metastasis. However, the specific molecular mechanisms underlying this relationship remain to be unveiled. In this study, we assessed the impact of gastrin and the Wnt/β-catenin inhibitor XAV939 on the epithelial-mesenchymal transition (EMT) of the SGC-7901 and MKN45 GC cell lines, and we determined that gastrin-17 significantly decreased E-cadherin expression and upregulated the expression of Snail1 and N-cadherin in GC cells. In addition, gastrin 17 also significantly increased the expression of Wnt3α in a dose-dependent manner. Consistent with these results, gastrin-17 promoted GC cell invasion, proliferation, and migration in a dose-dependent fashion, and these effects were inhibited by XAV939. Together, these results indicated that gastrin-17 induced GC cell EMT, migration, and invasion via the Wnt/β-catenin signaling pathway, which suggests that this gastrin/Wnt/β-catenin signaling axis may represent a therapeutic target for the prevention of GC metastasis.