Downregulation of PTPRK Promotes Cell Proliferation and Metastasis of NSCLC by Enhancing STAT3 Activation.

Xuting Xu,Lishan Min,Dong Li,Zhihong Ma,Jin Liu,Licheng Dai,Shunli Dong,Huilian Huang

doi:10.1155/2019/4265040

Xuting Xu, Lishan Min + Show 6 more

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https://doi.org/10.1155/2019/4265040

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Journal: Analytical Cellular Pathology	Publication Date: Jan 29, 2019
Citations: 5	License type: CC BY 4.0

Affiliation: Huzhou Central Hospital

Abstract

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.

Highlights

Lung cancer, especially non-small-cell lung cancer (NSCLC), is the most frequent cause of cancer-related deaths [1]
Protein tyrosine phosphatase (PTPRK) Is Frequently Underexpressed in NSCLC with Lymph Node (LN) Metastasis
To establish the association between PTPRK expression and tumor metastasis, the PTPRK mRNA expression level was measured by Quantitative Real-Time PCR (qRT-PCR) analysis in 30 lung tumors with non-lymph node metastasis and 16 tumors with lymph node metastasis

Summary

Introduction

Especially non-small-cell lung cancer (NSCLC), is the most frequent cause of cancer-related deaths [1]. The 5-year survival rate of lung cancer has not significantly increased [3]. In the past few decades, multiple oncogenes and tumor-suppressive genes have been discovered in the biological processes that regulate lung tumorigenesis. Alterations in tyrosine phosphorylation patterns are a common phenomenon in various human cancers, including lung cancer. Recent studies have shown that PTPRK is frequently downregulated in many human cancers. Recent studies show that PTPRK is frequently underexpressed in NKTCL and contributes to NKTCL pathogenesis [9,10,11]. Some studies have shown that the expression of PTPRK was significantly downregulated in lung cancer-derived cell lines, its Analytical Cellular Pathology contribution to aberrant signaling in lung cancers remains largely unexploited [12]

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Results

Conclusion