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

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 sti...

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Bibliographic Details
Published in:OncoTargets and therapy 2018-01, Vol.11, p.7795-7803
Main Authors: Tian, Xiang'an, Yang, Chengju, Yang, Liguang, Sun, Qinli, Liu, Naiqing
Format: Article
Language:English
Subjects:
Adenocarcinoma
Analysis
Biotechnology
Breast cancer
Cancer
Cell differentiation
Cell growth
Colorectal cancer
Cytological research
Development and progression
Gastric cancer
Immunohistochemistry
Kinases
Liver cancer
Lung cancer
Medical prognosis
Medical research
Metastasis
Non-small cell lung cancer
Original Research
Ovarian cancer
Phenols (Class of compounds)
Phosphatase
Phosphatases
Phosphorylation
Proteins
Small cell lung cancer
Stomach cancer
Tumors
Tyrosine
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Summary: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. 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. 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. In conclusion, patients with lower PTPRF expression in gastric adenocarcinoma tissues were more predisposed to advanced tumor stage and unfavorable prognosis.
ISSN:1178-6930
1178-6930
DOI:10.2147/OTT.S178152