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PTPRF as a novel tumor suppressor through deactivation of ERK1/2 signaling in gastric adenocarcinoma

Authors Tian X, Yang C, Yang L, Sun Q, Liu N

Received 25 June 2018

Accepted for publication 3 September 2018

Published 2 November 2018 Volume 2018:11 Pages 7795—7803

DOI https://doi.org/10.2147/OTT.S178152

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Justinn Cochran

Peer reviewer comments 2

Editor who approved publication: Dr Yao Dai


Xiang’an Tian,1 Chengju Yang,2 Liguang Yang,1 Qinli Sun,1 Naiqing Liu1

1First Department of General Surgery, Linyi Central Hospital, Linyi 276400, Shandong Province, China; 2Second Department of Obstetrics, Linyi Central Hospital, Linyi 276400, Shandong Province, China

Background: Protein tyrosine phosphatase, receptor type F (PTPRF) is an important phosphatase playing roles in regulating cell growth, differentiation and oncogenic transformation. Overexpression of PTPRF has been observed in non-small cell lung cancer, but its clinical significance in other malignancies is still unknown.
Methods: We explored the expression pattern of PTPRF in gastric adenocarcinoma by using RT-qPCR and immunohistochemistry staining. The clinical significance of PTPRF was evaluated by univariate and multivariate analyses. Furthermore, the signaling pathways downstream of PTPRF was investigated by knockdown and overexpression assays combined with cellular studies.
Results: We found a remarkable down-regulation of PTPRF in gastric adenocarcinomas, which was significantly associated with advanced tumor TNM stages. Survival analysis showed that lower PTPRF level indicated a poorer overall survival of gastric adenocarcinoma patients. By conducting knockdown and overexpression studies in gastric adenocarcinoma cells, we revealed the role of PTPRF on inhibiting extracellular signal-regulated kinase-1/2 (ERK1/2) phosphorylation and its downstream signaling. Consistent with clinical findings, cellular results demonstrated that overexpressing PTPRF can significantly inhibit tumor migration and invasion, while silencing PTPRF showed opposite effects.
Conclusion: In conclusion, patients with lower PTPRF expression in gastric adenocarcinoma tissues were more predisposed to advanced tumor stage and unfavorable prognosis.

Keywords: gastric cancer, PTPRF, prognosis, invasion

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