Abstract
Previous studies showed that aberrant Serine/threonine/tyrosine kinase 1 (STYK1, also known as NOK) or/and E-cadherin were involved in the progression of some types of human cancers. However, whether they contributed to the development of pancreatic cancer was unknown. Here, we investigated the prognostic significance of aberrant STYK1 and E-cadherin in pancreatic cancer. Our results showed that STYK1 expression increased while E-cadherin decreased in pancreatic cancer tissues compared with normal pancreas tissues. STYK1 level was positively correlated with lymph node metastasis and clinical stage in pancreatic cancer patients. E-cadherin expression was inversely correlated with STYK1 expression in pancreatic cancer tissue samples. Patients with high STYK1 and low E-cadherin expression had the worst prognosis. In addition, STYK1 knockdown in pancreatic cancer cell lines inhibited cell proliferation, enhanced cell apoptosis, induced cell cycle arrest, and prohibited cell migration, while STYK1 over-expression showed the opposite effects. Silencing STYK1 also increased E-cadherin expression and inhibited epithelial-to-mesenchymal transition (EMT) and p-p38 expression in vitro. Over-expression had showed the opposite trends, and treatment with p38 inhibitor, SB203580, could reverse the trends. Thus, STYK1 repressed E-cadherin expression and promoted EMT, mediated by p38 MAPK signaling pathway, which was the possible mechanism for STYK1-mediated pancreatic cancer cell proliferation and migration. In summary, our results showed that STYK1 might be a prognostic marker for pancreatic cancer patients and might be a novel strategy for the treatment of pancreatic cancer.
Highlights
Pancreatic cancer, a lethal malignancy worldwide, is estimated that 53,670 new cases of pancreatic cancer patients were diagnosed in the United States in 2017[1]
Serine/threonine/tyrosine kinase 1 (STYK1) and E-cadherin mRNA expression were detected by semi-quantitative RT-PCR in 20 cases of pancreatic cancer tissue samples and paired adjacent normal tissue samples
To further investigate the association of survival time with E-cadherin and STYK1 expression, a final concomitant model was constructed and we found that a combinatorial pattern of high E-cadherin expression and low STYK1 predicted the better clinical prognosis in pancreatic cancer (Figure 4C, 4D)
Summary
Pancreatic cancer, a lethal malignancy worldwide, is estimated that 53,670 new cases of pancreatic cancer patients were diagnosed in the United States in 2017[1]. Pancreatic cancer progressed extremely fast at the advanced stage. It is very hard to detect the disease at the early stage due to the lack of obvious www.impactjournals.com/oncotarget been recommended in the National Comprehensive Cancer. We wonder if there is any other gene that belongs to tyrosine kinase or its receptor could work as what erlotinib has done in the clinics. Threonine/tyrosine kinase 1 (STYK1) is a human putative protein kinase that belongs to the receptor protein tyrosine kinase family [3, 4]. Previous studies have found that STYK1 could promote tumorigenesis through enhancing epithelial-tomesenchymal transition (EMT) [11].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
