Abstract
Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. However, the molecular mechanisms underlying NSCLC progression remains not fully understood. In this study, 347 patients with complete clinicopathologic characteristics who underwent NSCLC surgery were recruited for the investigation. We verified that elevated serine threonine tyrosine kinase 1 (STYK1) or decreased serine peptidase inhibitor Kunitz type 2 (SPINT2/HAI-2) expression significantly correlated with poor prognosis, tumor invasion, and metastasis of NSCLC patients. STYK1 overexpression promoted NSCLC cells proliferation, migration, and invasion. STYK1 also induced epithelial–mesenchymal transition by E-cadherin downregulation and Snail upregulation. Moreover, RNA-seq, quantitative polymerase chain reaction (qRT-PCR), and western blot analyses confirmed that STYK1 overexpression significantly decreased the SPINT2 level in NSCLC cells, and SPINT2 overexpression obviously reversed STYK1-mediated NSCLC progression both in vitro and in vivo. Further survival analyses showed that NSCLC patients with high STYK1 level and low SPINT2 level had the worst prognosis and survival. These results indicated that STYK1 facilitated NSCLC progression via reducing SPINT2 expression. Therefore, targeting STYK1 and SPINT2 may be a novel therapeutic strategy for NSCLC.
Highlights
Serine threonine tyrosine kinase 1 (STYK1), known as NOK, was identified as a new member of the receptor protein tyrosine kinase (RPTK)-like protein family[1]
We analyzed 994 Non-small cell lung cancer (NSCLC) cases via Kaplan–Meier analysis in The Human Protein Atlas, and we found high STYK1 expression was related to poor prognosis (Fig. 1b)
The Kaplan–Meier plotter database analysis showed the positive correlation between high STYK1 expression and poor prognosis of NSCLC patients (HR = 1.44, Logrank P = 0.034, Fig. 1c)
Summary
Serine threonine tyrosine kinase 1 (STYK1), known as NOK, was identified as a new member of the receptor protein tyrosine kinase (RPTK)-like protein family[1]. Like other RPTKs’ actions on promoting cancer progression[2], STYK1 had been reported to promote cell proliferation of BaF3 cells. Numerous studies suggested SPINT2 acted as a tumor suppressor[13], and inhibited cancer cell proliferation, metastasis, and invasion[10,11,14]. Ma et al Cell Death and Disease (2019)10:435 including lung[11]. Decreased SPINT2 expression has been found in several human cancers, such as liver cancer[15], breast cancer[16], prostate cancer[17], ovarian cancer[18], and cervical cancer[19]. The SPINT2 expression and its role in lung cancer are still unknown
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