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Downregulation of PTPRK Promotes Cell Proliferation and Metastasis of NSCLC by Enhancing STAT3 Activation
Xuting Xu1, Dong Li2, Jin Liu3
1Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Huzhou, Zhejiang 313000, China.
Objective:
The receptor-type tyrosine-protein phosphatase κ (PTPRK) is a candidate tumor suppressor involved in the tumorigenesis of various organs. However, its expression and biological roles in non-small-cell lung cancer (NSCLC) have not yet been investigated.
Methods:
PTPRK expression in NSCLC tissues and cell lines was examined using real-time PCR and western blotting. In addition, the effects of PTPRK on cell migration, invasion, and proliferation were evaluated in vitro. Furthermore, we explored whether the downregulation of PTPRK led to STAT3 activation in NSCLC cell lines by western blotting. The expression of phospho-STAT3Tyr705 in primary human NSCLC tissues was evaluated by immunohistochemistry.
Results:
The results showed that PTPRK expression was frequently reduced in NSCLC tissues with lymph node metastasis and cell lines. The inhibition of PTPRK expression resulted in increased proliferation, invasion, and migration of NSCLC cells in vitro. Additionally, after silencing of PTPRK, phospho-STAT3Tyr705 was significantly increased in NSCLC cells. Moreover, the phospho-STAT3Tyr705 levels of NSCLC tissues were positively correlated with lymph node metastasis and significantly inversely correlated with the expression of PTPRK (p < 0.05).
Conclusions:
These results suggested that PTPRK functions as a novel tumor suppressor in NSCLC, and its suppressive ability may be involved in STAT3 activation.
Insights
Receptor-type tyrosine-protein phosphatase kappa (PTPRK) acts as a tumor suppressor in non-small-cell lung cancer (NSCLC). Its reduced expression promotes NSCLC progression and STAT3 activation.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Receptor-type tyrosine-protein phosphatase kappa (PTPRK) is implicated as a tumor suppressor in various cancers.
- The role of PTPRK in non-small-cell lung cancer (NSCLC) remains unexplored.
Purpose of the Study:
- To investigate the expression and function of PTPRK in NSCLC.
- To determine the relationship between PTPRK, cell behavior, and STAT3 signaling in NSCLC.
Main Methods:
- Quantitative real-time PCR and western blotting assessed PTPRK expression in NSCLC tissues and cell lines.
- In vitro assays evaluated the impact of PTPRK on cell proliferation, migration, and invasion.
- Western blotting and immunohistochemistry analyzed STAT3 activation (phospho-STAT3Tyr705) in relation to PTPRK expression and lymph node metastasis.
Main Results:
- PTPRK expression was significantly downregulated in NSCLC tissues with lymph node metastasis and in NSCLC cell lines.
- PTPRK inhibition enhanced NSCLC cell proliferation, invasion, and migration.
- PTPRK silencing led to increased phospho-STAT3Tyr705 levels, which correlated positively with lymph node metastasis and inversely with PTPRK expression.
Conclusions:
- PTPRK functions as a novel tumor suppressor in NSCLC.
- The tumor-suppressive role of PTPRK in NSCLC may involve the modulation of STAT3 activation.
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