NPTX1 promotes metastasis via integrin/FAK signaling in gastric cancer
Received 30 November 2018
Accepted for publication 4 February 2019
Published 15 April 2019 Volume 2019:11 Pages 3237—3251
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Professor Nakshatri
Hongfei Yan,1,2,* Chunlei Zheng,1,2,* Zhi Li,1,2 Bowen Bao,1,2 Bowen Yang,1,2 Kezuo Hou,1,2 Xiujuan Qu,1,2 Jiawen Xiao,3 Xiaofang Che,1,2 Yunpeng Liu1,2
1Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, China; 2Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, The First Hospital of China Medical University, Shenyang 110001, China; 3Department of Medical Oncology, Shenyang Fifth People Hospital, Tiexi District, Shenyang 110001, China
*These authors contributed equally to this work
Purpose: This study aimed to investigate the effect of NPTX1 on the prognosis of gastric cancer (GC), as well as the metastatic process in GC.
Materials and methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to analyze the association between NPTX1 expression and prognosis in GC. Quantitative real-time polymerase chain reaction and Western blots were applied to examine the expression of NPTX1 in GC cell lines and expression of genes in downstream pathways. The role of NPTX1 on the migration, invasion, adhesion, and proliferation of GC cell lines was investigated with the transwell assay, the adhesion assay, and the MTT assay. Immunofluorescence staining was used to observe the effect of NPTX1 knockdown on the morphology of cells.
Results: According to the review of TCGA and GEO databases of GC, we found that the expression of NPTX1 increased in cancer tissues and high NPTX1 expression was correlated with poor overall survival, which was associated with lymph node stage in clinicopathologic parameters. Knockdown of NPTX1 attenuated the migration, invasion, and adhesion abilities of GC cells. According to gene set enrichment analysis, NPTX1 was found to be positively related to integrin and focal adhesion (FA). Additionally, NPTX1 knockdown decreased the expression of integrin α1 and integrin α7, followed by deregulation of the expression of p-Src, p-Akt, p-Erk, MMP2, and MMP7, as well as inhibiting the formation of FA complexes and decreasing the length of pseudopods in GC cells.
Conclusion: Our study provides strong evidence that NPTX1 plays a crucial role in promoting metastasis and acts as a prognostic indicator in GC.
Keywords: gastric cancer, NPTX1,metastasis, integrin
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